RESUMEN
Here, we analysed the use of Vbeta-TCR regions by CD4+ and CD8+ T cells from acute and chronic chagasic patients using flow cytometry. We determined the Vbeta expression in cells freshly isolated from patients, as well as after in vitro stimulation with antigens derived from epimastigote (EPI) or trypomastigote (TRYPO) forms of Trypanosoma cruzi. Analysis of Vbeta-TCR expression of T cells freshly isolated from patients showed a decrease in Vbeta5 expression in the CD4+ T-cell population from acutely infected individuals, whereas CD4+Vbeta5+ T cells were found to be increased in chronic patients with the cardiac, but not indeterminate, clinical form. After culturing peripheral blood mononuclear cells (PBMC) from chronic patients with EPI or TRYPO, we found that both antigenic preparations led to a preferential expansion of CD4+Vbeta5+ T cells. EPI stimulation also led to the expansion of CD8+Vbeta5+ T cells, whereas TRYPO led to the expansion of this cell population only if PBMC were from cardiac and not indeterminate patients. We observed that TRYPO stimulation led to an increase in the frequency of CD4+Vbeta17+ T cells in cultures of PBMC from indeterminate patients, whereas an increase in the frequency of CD8+Vbeta17+ T cells was found upon TRYPO stimulation of PBMC from cardiac patients. Despite this increase in the frequency of Vbeta17+ T-cell populations upon TRYPO stimulation, the same antigenic preparation led to a much higher expansion of Vbeta5+ T cells. These results show a differential expression of Vbeta5-TCR in cells freshly isolated from chagasic patients in different stages of the disease and that parasite-specific antigens stimulate a portion of the T-cell repertoire with preferential usage of Vbeta5-TCR.
Asunto(s)
Enfermedad de Chagas/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Linfocitos T/inmunología , Enfermedad Aguda , Animales , Antígenos de Protozoos/inmunología , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Enfermedad Crónica , Cardiopatías/inmunología , Humanos , Trypanosoma cruzi/inmunologíaRESUMEN
Cellular and humoral immune responses to Schistosoma mansoni antigen preparations were evaluated in individuals presumed to be susceptible or resistant to reinfection after chemotherapeutic cure. A consistent proliferative increase in the response to soluble egg antigen (SEA) was observed post-treatment in both the susceptible and resistant groups. However, this change was not related to resistance. Isotype studies showed that IgM antibody levels to soluble worm antigen preparation (SWAP) and cercariae antigens were significantly higher in the resistant group than in the susceptible group. Post-treatment, an increase in IgE anti-SWAP and anti-schistosomular tegument (STEG) responses and a decrease in IgG4 anti-SEA and anti-STEG responses were observed in the resistant group. These finding are similar to those we have reported previously for a putative resistant group termed endemic normals, and are compatible with immunologic studies in different endemic areas. Together, these findings indicate that even on the population level, high IgE specificities coupled with low IgG4 specificities correlate well with documented resistance to reinfection.
Asunto(s)
Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos Antihelmínticos/sangre , Antígenos Helmínticos/inmunología , Antimaláricos/uso terapéutico , Brasil/epidemiología , Niño , Preescolar , Susceptibilidad a Enfermedades/inmunología , Femenino , Humanos , Inmunidad Celular , Isotipos de Inmunoglobulinas/sangre , Masculino , Ratones , Persona de Mediana Edad , Oxamniquina/uso terapéutico , Prevalencia , Recurrencia , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/epidemiologíaRESUMEN
It has previously been demonstrated that Trypanosoma cruzi-derived antigens (TRP) and human parasite-specific antibodies (Id) stimulate proliferation of cells from Chagasic patients. More recently, we have shown that activated T cells and CD5+ B cells are present in elevated levels in the peripheral blood of Chagasic patients. Upon in vitro exposure to these two different types of stimulatory molecules (TRP, Id), we now show that each of these elevated populations respond differentially to TRP or Id. We found that stimulation with TRP led to preferential expansion of activated T cells, while Id preferentially stimulated CD5+ B cells and CD8+ T cells. Moreover, this expansion of CD5+ B cells by Id was even more pronounced in cultures of cells from Chagasic patients with the severe, cardiac form of the disease, as compared to indeterminate patients. CD8+ T cells comprise approximately 50% of the total T cells in cultures stimulated by Id while in TRP-stimulated cultures their frequency is proportionally lower. Since parasite antigens and antiparasite antibodies are always present in the host during the chronic phase of the disease, they may also be involved with differential activation mechanisms of these cell populations in vivo.
Asunto(s)
Subgrupos de Linfocitos B/inmunología , Antígenos CD5/metabolismo , Enfermedad de Chagas/inmunología , Linfocitos T/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos Antiprotozoarios/administración & dosificación , Antígenos de Protozoos/administración & dosificación , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Humanos , Técnicas In Vitro , Interferón gamma/biosíntesis , Interleucina-10/biosíntesis , Activación de Linfocitos , Persona de Mediana Edad , Trypanosoma cruzi/inmunologíaRESUMEN
The opportunities and challenges for the study and control of parasitic diseases in the 21st century are both exciting and daunting. Based on the contributions from this field over the last part of the 20th century, we should expect new biologic concepts will continue to come from this discipline to enrich the general area of biomedical research. The general nature of such a broad category of infections is difficult to distill, but they often depend on well-orchestrated, complex life cycles and they often involve chronic, relatively well-balanced host/parasite relationships. Such characteristics force biological systems to their limits, and this may be why studies of these diseases have made fundamental contributions to molecular biology, cell biology and immunology. However, if these findings are to continue apace, parasitologists must capitalize on the new findings being generated though genomics, bioinformatics, proteomics, and genetic manipulations of both host and parasite. Furthermore, they must do so based on sound biological insights and the use of hypothesis-driven studies of these complex systems. A major challenge over the next century will be to capitalize on these new findings and translate them into successful, sustainable strategies for control, elimination and eradication of the parasitic diseases that pose major public health threats to the physical and cognitive development and health of so many people worldwide.
Asunto(s)
Alergia e Inmunología/tendencias , Biología Molecular/tendencias , Enfermedades Parasitarias/prevención & control , Investigación/tendencias , Toma de Decisiones , Predicción , Humanos , Práctica de Salud PúblicaRESUMEN
Exposure of neonatal mice to appropriate, cross-reactive Id (CRI) preparations alters immune responsiveness, ameliorates pathology, and prolongs survival of animals upon subsequent Schistosoma mansoni infection. However, because schistosome infections profoundly affect host immunobiology, which responses are effected by neonatal Id exposure alone and which responses are influenced by infection is unclear. To directly examine the schistosome soluble egg Ag (SEA)-specific immune responses altered by CRI exposure, neonatal mice were injected with CRI-expressing (CRI+) SEA-specific Ab preparations, SEA-specific Abs that did not express CRI (CRI-), or normal mouse Ig. At 9 wk of age, only mice that were neonatally exposed to CRI+ anti-SEA Abs displayed significant SEA-specific IgG serum levels and spleen cell proliferative responses. SEA-stimulated spleen cells from these CRI+-exposed mice also produced IFN-gamma, although not at significantly higher levels than mice receiving CRI- Id or normal mouse Ig. If CRI+-exposed mice were also injected with SEA at 8 wk of age, the 9-wk IFN-gamma responses were significantly higher than those of the other neonatal injection groups. The presence of both CRI and anti-CRI in the sera of animals neonatally injected with CRI, but receiving no exposure to S. mansoni Ags or infection, suggested a functional idiotypic network led to these responses. These data demonstrate that appropriate idiotypic exposure induces B and T cell responsiveness to the Ag recognized by the Id and support the hypothesis that neonatal idiotypic exposure can be an important immunoregulatory factor in schistosomiasis.
Asunto(s)
Animales Recién Nacidos/inmunología , Anticuerpos Antihelmínticos/biosíntesis , Antígenos Helmínticos/inmunología , Complejo CD3 , Inmunización Pasiva , Idiotipos de Inmunoglobulinas/inmunología , Óvulo/inmunología , Schistosoma mansoni/inmunología , Animales , Anticuerpos Antiidiotipos/sangre , Antígenos Helmínticos/farmacología , Reacciones Cruzadas , Femenino , Sueros Inmunes/farmacología , Inmunidad Celular , Inmunización Pasiva/métodos , Idiotipos de Inmunoglobulinas/administración & dosificación , Inyecciones Intraperitoneales , Ratones , Ratones Endogámicos CBA , Conejos , Receptores de Antígenos de Linfocitos T/inmunología , Bazo/citología , Bazo/inmunologíaRESUMEN
The current study has compared the activation status and the expression of the CD28 molecule on circulating CD4+ and CD8+ lymphocytes from patients with different clinical forms of schistosomiasis. The data show that patients with acute schistosomiasis have an increase on the mean percentage of CD4+ HLA-DR+ cells, whereas chronic asymptomatic patients exhibit an increased mean percentage of CD8+ HLA-DR+ cells. Patients with the hepatosplenic disease showed an increase in both CD4+ HLA-DR+ and CD8+ HLA-DR+ cells. Despite the high levels of CD8+ HLA-DR+ cells in hepatosplenic patients, they presented a decreased ratio of CD8+ CD28+/CD8+ cells. These findings of a different percentage of circulating CD8+ CD28+ cells might explain the different in vitro cellular reactivity of asymptomatic and hepatosplenic patients and the defects in the cytokine secretion patterns reported in individuals with hepatosplenic schistosomiasis.
Asunto(s)
Antígenos CD28/inmunología , Activación de Linfocitos , Esquistosomiasis mansoni/inmunología , Subgrupos de Linfocitos T/inmunología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Estudios de Casos y Controles , Niño , Enfermedad Crónica , Citometría de Flujo , Antígenos HLA-DR/inmunología , Humanos , Parasitosis Hepáticas/inmunología , Persona de Mediana Edad , Enfermedades del Bazo/inmunología , Enfermedades del Bazo/parasitologíaRESUMEN
Complementary DNA, encoding the mitochondrial enzyme NADH-ubiquinone oxidoreductase subunit 5 (SmND5) of the human parasite Schistosoma mansoni was isolated by screening a S. mansoni cDNA library with a human androgen receptor (hAR) cDNA probe. The complete nucleotide and deduced aminoacid sequences of SmND5 were determined. Southern blot analysis revealed the occurrence of a single copy gene for SmND5 and by means of RT-PCR, it was shown that sex- and stage-specific expression of SmND5 occurred. In order to establish a functional relationship between the mitochondrial enzyme and the androgen receptor, the effects of testosterone were compared to those of classical respiratory chain inhibitors, using adult schistosome and beef heart submitochondrial particles. Physiological concentrations of testosterone were able to inhibit the maintenance of proton gradient across the mitochondrial membranes, as well as ATP synthesis. The steroid was found to be cytotoxic to the larvae, but not to adult schistosomes. A model is proposed to explain the observed in vivo testosterone-related differences in worm burdens, in experimental chronic infections.
Asunto(s)
Mitocondrias Cardíacas/metabolismo , NADH NADPH Oxidorreductasas/química , NADH NADPH Oxidorreductasas/genética , Schistosoma mansoni/enzimología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Abejas/enzimología , Caenorhabditis elegans/enzimología , Bovinos , Clonación Molecular , Secuencia de Consenso , ADN Complementario , Complejo I de Transporte de Electrón , Biblioteca de Genes , Humanos , Mitocondrias Cardíacas/efectos de los fármacos , Datos de Secuencia Molecular , NADH NADPH Oxidorreductasas/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Receptores Androgénicos/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Schistosoma mansoni/genética , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Partículas Submitocóndricas/efectos de los fármacos , Partículas Submitocóndricas/metabolismo , Testosterona/farmacologíaRESUMEN
People infected with Trypanosoma cruzi remain so for life, yet only 30-40% of these individuals develop characteristic chagasic cardiomyopathies. Similarly, when infected with the Brazilian strain of T. cruzi, DBA/2 mice develop severe cardiac damage while B10.D2 mice do not. To better understand the immunological parameters that may be involved in the disease process, we have used this murine model (DBA/2 vs B10.D2) and compared the changes in cytokine production during the course of infection with T cruzi. Concanavalin A (Con A) stimulation of spleen cells harvested during the acute phase (day 30) resulted in similarly high levels of IFN-gamma in both mouse strains. However, the amount of IFN-gamma in supernatants from cultures of B10.D2 spleen cells initiated during the chronic phase (day 72) was at subacute levels, whereas secretion by chronic DBA/2 spleen cells remained high. In addition, Con A-stimulated spleen cells from acute DBA/2 mice produced approximately twice as much IL-10 and significantly more IL-4 than cells from B10.D2 mice. IL-4 secretion remained low by cells from chronic B10.D2 mice, but when using cells from chronic DBA/2 mice, levels continued to increase beyond the already high levels secreted by cells harvested during the acute phase. Proliferative responses to Con A stimulation by spleen cells from DBA/2 mice were significantly higher than those from B10.D2 mice in both the acute and chronic phases. These data suggest that enhanced responses in DBA/2 mice, which may be related to a higher parasite burden, a lack of down-regulation, and/or the onset of autoimmune phenomena, correlate with the more severe cardiomyopathy seen in pathopermissive mice.
Asunto(s)
Enfermedad de Chagas/inmunología , Citocinas/fisiología , Modelos Animales de Enfermedad , Animales , Interferón gamma , Interleucina-10 , Interleucina-4 , Ratones , Ratones Endogámicos DBAAsunto(s)
Oxamniquina/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Adolescente , Adulto , Animales , Antiparasitarios/farmacología , Brasil , Niño , Preescolar , Protocolos Clínicos , Estudios Transversales , Estudios de Seguimiento , Humanos , Inmunidad Innata , Persona de Mediana Edad , Schistosoma mansoni/patogenicidadRESUMEN
People infected with Trypanosoma cruzi remain so for life, yet only 30-40 percent of these individuals develop characteristic chagasic cardiomyopathies. Similarly, when infected with the Brazilian strain of T. cruzi, DBA/2 mice develop severe cardiac damage while B10.D2 mice do not. To better understand the immunological parameters that may be involved in the disease process, we have used this murine model (DBA/2 vs B10.D2) and compared to changes in cytokine production during the course of infection with T. cruzi. Concanavalin A (Con A) stimulation of spleen cells harvested during the acute phase (day 30) resulted in similarly high levels of IFN-gamma in both mouse strains. However, the amount of IFN-gamma in supernatants from cultures of B10.D2 spleen cells initiated during the chronic phase (day 72) was at subacute levels, whereas secretion by chronic DBA/2 spleen cells remained high. In addition, Con A-stimulated spleen cells from acute DBA/2 mice produced approximately twice as much IL-10 and significantly more IL-4 than cells from B10.D2 mice. IL-4 secretion remained low by cells from chronic B10.D2 mice, but when using cells from chronic DBA/2 mice, levels continued to increase beyond the already high levels secreted by cells harvested during the acute phase. Proliferative responses to Con A stimulation by spleen cells from DBA/2 mice were significantly higher than those from B10.D2 mice in both the acute and chronic phases. These data suggest that enhanced responses in DBA/2 mice, which may be related to a higher parasite burden, a lack of down-regulation, and/or the onset of autoimmune phenomena, correlate with the more severe cardiomyopathy seen in pathopermissive mice.
Asunto(s)
Ratones , Animales , Enfermedad de Chagas/inmunología , Enfermedad de Chagas/fisiopatología , Citocinas/fisiología , Modelos Animales de Enfermedad , Interferón gamma , Interleucina-10 , Interleucina-4 , Ratones Endogámicos DBARESUMEN
The role of cytokines on the in vitro proliferative response of peripheral blood mononuclear cells (PBMC) from Schistosoma mansoni infected patients to soluble egg (SEA) and adult worm antigens (SWAP) were evaluated. The results obtained demonstrated that the proliferative response of PBMC from chronic intestinal (INT) patients to SEA and SWAP is increased by the blockage of IL-10 with specific monoclonal antibodies (MAb). The effects of these antibodies were readily reversed by the addition of recombinant IL-10. In contrast, no effect was observed on the PBMC response of acute and hepatosplenic patients (HS) in the presence of anti-IL-10. Anti-IL-4 antibodies decreased the PBMC response of the intestinal (INT) and HS individuals to SEA and SWAP, and the PBMC response of acute patients to SEA but not to SWAP. Addition of anti-IL-5 MAb did not decrease the PBMC response of acute patients to SEA or SWAP. These results suggested that IL-10 has an important role in the modulation of the immune response in chronic asymptomatic patients and that this cytokine may be an important factor in controlling morbidity.
Asunto(s)
Citocinas/fisiología , Leucocitos Mononucleares/inmunología , Schistosoma mansoni/inmunología , Enfermedad Aguda , Animales , Anticuerpos Monoclonales/farmacología , Antígenos Helmínticos/farmacología , Células Cultivadas , Enfermedad Crónica , Femenino , Humanos , Interleucina-10/fisiología , Interleucina-4/inmunología , Interleucina-4/fisiología , Interleucina-5/inmunología , Interleucina-5/fisiología , Parasitosis Intestinales/inmunología , Parasitosis Hepáticas/inmunología , Activación de Linfocitos , Masculino , Ratones , Schistosoma mansoni/crecimiento & desarrollo , Esquistosomiasis mansoni/inmunología , Enfermedades del Bazo/inmunologíaRESUMEN
The aim of this study was to examine three distinct groups of schistosomiasis patients and to determine whether cell phenotype profiles could be correlated with the different clinical forms of the disease. The data obtained indicate that Schistosoma mansoni infected patients have a lower percentage of CD3+ T cells than do non-infected individuals. Interestingly, infected patients presented more than twice the mean percentage of circulating activated T cells (CD3+HLA-DR+) when compared to the control group. Examination of T lymphocyte subpopulations showed that patients with the severe hepatosplenic form (HS) of the disease had lower levels of both CD8High+ and CD8Low+ cells when compared to the other groups of patients. All infected individuals had a higher percentage of circulating B cells, with an increase in the CD5+ B cell population that was more evident in the HS group. The data presented here are evidence to support a relationship between the hepatosplenic form of the disease, a decrease on the CD8+ cell population and an elevation on CD5+ B cells.
Asunto(s)
Linfocitos B/inmunología , Esquistosomiasis mansoni/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , Animales , Antígenos CD/inmunología , Niño , Heces/parasitología , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Recuento de Huevos de Parásitos , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/clasificaciónRESUMEN
Inbred male CBA/J mice with chronic Schistosoma mansoni infections develop two distinct syndromes. Hypersplenomegaly syndrome (HSS) demonstrates pathologic similarities to the hepatosplenic form of chronic human schistosomiasis, and moderate splenomegaly syndrome (MSS) resembles the asymptomatic intestinal form. Immunoaffinity-purified Abs against S. mansoni soluble egg Ags (SEA) from infected patients' sera differ idiotypically according to the donor's clinical form of the disease. We now show that immunoaffinity-purified anti-SEA Abs (Id) from MSS or HSS mice parallel idiotypic preparations of the analogous human clinical form by their differential ability to stimulate the proliferation of anti-Id T cells. MSS Id preparations stimulate spleen cells from either MSS or HSS animals. In contrast, HSS Id does not stimulate spleen cells from either group. In an anti-SEA ELISA, MSS and HSS Id preparations contained comparable levels of IgM and IgG1. However, the MSS Id preparation had higher levels of SEA-specific IgG2a and IgG2b than did HSS Id. The Ig isotypes of these Id preparations suggested differences in cytokine expression patterns. Studies of the cytokine profiles of the spleen cells responding to anti-SEA Id preparations demonstrated that while Id preparations from acutely infected mice stimulate IL-4 and IL-10 production, Id preparations from chronic MSS mice stimulate IFN-gamma production. HSS Id did not stimulate the production of any of these cytokines. The possibility that distinct immunoregulatory environments may contribute to the development of MSS and HSS correlates with earlier hypotheses that hepatosplenic pathology results at least in part from a lack of development or expression of appropriate regulatory Ids.
Asunto(s)
Anticuerpos Antiidiotipos/inmunología , Anticuerpos Antihelmínticos/inmunología , Antígenos Helmínticos/inmunología , Citocinas/inmunología , Schistosoma mansoni , Esquistosomiasis mansoni/inmunología , Células TH1/inmunología , Adyuvantes Inmunológicos , Animales , Humanos , Isotipos de Inmunoglobulinas , Masculino , Ratones , Ratones Endogámicos CBARESUMEN
The aim of this study is to evaluate the effects of parasite clearance on the immunological profile of peripheral blood mononuclear cells (PBMC) from chagasic patients submitted to specific drug therapy. PBMC were examined by flow cytometry and proliferative responsiveness to Trypanosoma cruzi-related stimuli. Three groups of patients were studied: not treated (NT), treated not cured (TNC) and cured (C). All data were compared to values from uninfected individuals (NI). NT displayed a lower percentage of CD3+ cells as compared to NI, while TNC and C had mean values that were between those from NI and NT. Infected patients had double the percent of CD3+ HLA-DR+ cells, independent of the efficacy of the treatment. Thus, absence of circulating parasites did not reduce T cell activation in Chagas' disease. NT displayed a higher percentage of CD5+ B cells as compared to NI, while TNC and C had mean values between those from NI and NT. In contrast to the phenotypic data, the in vitro mean proliferative responses to parasite-related stimuli of PBMC from C were reduced to the low mean levels observed in NI. These striking differences were statistically different from the high responses seen in NT and TNC. Our data suggest that proliferative responses of PBMC from C reflect immunological changes due elimination of parasite. However, successful treatment did not alter the levels of peripheral T cell activation.
Asunto(s)
Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/inmunología , Leucocitos Mononucleares/inmunología , Tripanocidas/uso terapéutico , Adulto , Anciano , Animales , Antígenos de Protozoos , Linfocitos B/inmunología , Antígenos CD5/metabolismo , Enfermedad de Chagas/parasitología , Humanos , Técnicas In Vitro , Activación de Linfocitos , Persona de Mediana Edad , Fenotipo , Linfocitos T/inmunología , Trypanosoma cruzi/inmunología , Trypanosoma cruzi/aislamiento & purificaciónRESUMEN
A balanced host-parasite interaction during Trypanosoma cruzi infection allows for the establishment of a chronic infection that can last for many years. T cells are a major element responsible for parasite specific and non-specific immunity during the complex immune response of the host. However, the subpopulations of T cells involved in the response, as well as the exact mechanisms through which those cells are activated or rendered unresponsive, are not well defined. It is known that co-stimulatory signals, some of which are mediated via CD28, are of critical importance in the triggering of appropriate T cell responses. In this study the authors performed double-labelling studies to determine the frequency of expression of CD28 by CD4+ and CD8+ T lymphocytes in the peripheral blood of patients with Chagas' disease. The results show that chagasic patients throughout the spectrum of chronic clinical forms of the infection have significantly higher mean frequencies of CD4+CD28- and CD8+CD28-T cells, as compared with non-chagasic individuals. Considering the importance of CD28 for T-cell activation, the observed down-regulation or loss of CD28 during infection may indicate a possible basis for observed immunoregulatory events or distinct stages of T-cell activation in this infection. Recent evidence from patients with HIV/AIDS indicates that CD28- cell populations are more likely to undergo apoptosis, and increased apoptosis has been observed in experimental Chagas disease.
Asunto(s)
Antígenos CD28/biosíntesis , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Enfermedad de Chagas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales , Citometría de Flujo , Humanos , Activación de Linfocitos , Persona de Mediana EdadRESUMEN
The isotypic patterns of antibodies against Schistosoma mansoni antigenic preparations from eggs (SEA), adult worms (SWAP) and cercariae (CERC) have been studied in sera from two groups of individuals living in an area endemic for S. mansoni. One of the groups was comprised of individuals diagnosed as having S. mansoni infections based on their patency, i.e. those passing eggs in their faeces (patent infections, PI). The other group has been consider 'putatively resistant' due to their residence in an endemic area, their documented exposure to positive transmission sites, and their repeated negativity upon stool examinations (endemic normals, EN). There are strong specific responses of IgG1, IgG4 and IgM, particularly to SEA and CERC, by both groups. The reactivities of all isotypes were lower to SWAP. The responses of IgG4, IgM and IgE anti-CERC in EN and PI are higher than those found in normal individuals from outside endemic areas. In general, EN individuals express a relative higher level of anti-STEG IgE as compared to IgG4. On the other hand the pool of sera from PI showed the opposite pattern of higher IgG4 as compared to IgE. Several correlations are seen between isotypic responses to SEA, SWAP and CERC based on comparisons to the anti-SWAP IgE responses of the individuals in the two groups. These comparisons indicate the presence of distinct immunologic differences between individuals in the PI and the EN groups.
Asunto(s)
Anticuerpos Antihelmínticos/inmunología , Antígenos Helmínticos/inmunología , Isotipos de Inmunoglobulinas/inmunología , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/inmunología , Adulto , Anciano , Animales , Anticuerpos Antihelmínticos/análisis , Brasil , Niño , Ensayo de Inmunoadsorción Enzimática , Heces/parasitología , Femenino , Humanos , Inmunidad Innata , Isotipos de Inmunoglobulinas/análisis , Masculino , Persona de Mediana Edad , Recuento de Huevos de ParásitosRESUMEN
During human schistosomiasis host responses to antigens of various parasite life-cycle stages may contribute to whether the severe, hepatosplenic state develops or the patient remains relatively asymptomatic throughout infection, and may play a role in resistance. This study evaluated production of interferon gamma (IFN-gamma) in vitro by schistosome antigen-stimulated peripheral blood mononuclear cells (PBMCs) from asymptomatic patients, and by PBMCs from apparently uninfected, untreated persons living in areas endemic for Schistosoma mansoni ('endemic normals'). IFN-gamma production parallels PBMC proliferation in that schistosomal egg antigens stimulate patent patients' cells poorly, but strongly stimulate PBMCs from 'endemic normals'. This is proportionally true for antigens from adult worms and cercariae. Although asymptomatic patent patients' cells produced little or no IFN-gamma in response to the 3 schistosomal antigenic extracts, their PBMCs, and PBMCs from 'endemic normals', produced expected amounts of IFN-gamma when exposed to phytohaemagglutinin. This implies that persons with patent infections have schistosome antigen-specific defects in their ability to respond to IFN-gamma production that are not exhibited by putatively resistant 'endemic normals'.
Asunto(s)
Antígenos Helmínticos/inmunología , Interferón gamma/biosíntesis , Leucocitos Mononucleares/metabolismo , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/inmunología , Adulto , Animales , División Celular , Epítopos , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana EdadRESUMEN
Whole blood preparations from patients with either the indeterminate (asymptomatic) or cardiac clinical forms of chronic Trypanosoma cruzi infection were analyzed by flow cytometry using double-labeling to identify subsets of circulating lymphocytes. Several significant differences were demonstrated between the blood lymphocyte profiles of chagasic patients and non-chagasic controls. Clear increase in the percentages and actual numbers of double-positive cells of the phenotype CD3+/HLA-DR+, as well as decrease in the percentage of CD45RA+/CD4+ and CD45RA+/CD8+ T cells, indicate greater numbers of activated T cells circulating in the blood of infected patients. Consistent parallel increases were seen also in the B lymphocyte subset which stained double-positive for CD19/CD5. There were no significant differences in the circulation of these chronic chagasic patients in the CD4:CD8 ratios. Also, no substantive phenotypic differences were observed in the lymphocyte populations between the two ends of the clinical spectrum (indeterminate versus cardiac) in chronic human Chagas' disease. These observations demonstrate that increased levels of activated T cells and CD5+ B cells are present in the circulation of people with chronic Chagas' disease. These are cell phenotypes that have been associated in other conditions with autoimmune, polyclonal, and hyperimmune responses. The specificities of these activated cells and the roles they may play in resistance or pathogenesis during chronic Chagas' disease need now to be determined.
Asunto(s)
Subgrupos de Linfocitos B/inmunología , Enfermedad de Chagas/inmunología , Activación de Linfocitos/fisiología , Subgrupos de Linfocitos T/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/sangre , Relación CD4-CD8 , Enfermedad Crónica , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Antígenos HLA-DR/inmunología , Humanos , Persona de Mediana EdadRESUMEN
We have previously reported that heart lesions in patients with chronic cardiac Chagas' disease are composed predominantly of granzyme A+, cytolytic CD8+ T lymphocytes. We now pursue this study in the immunopathology of chronic chagasic cardiomyopathy by investigation of the expression of HLA antigens, and adhesion molecules in the hearts of seven chagasic patients with cardiac disease, two asymptomatic chagasic patients, and seven normal controls. Comparative immunohistochemical analyses show that HLA-ABC antigen expression is enhanced on the myocardial cells of chagasic patients with chronic cardiomyopathy, suggesting a possible role for these cells as targets for the CD8+ cytolytic lymphocytes dominant in these lesions. The HLA-DR antigens are not observed on myocardial cells, but are consistently upregulated on the endothelial cells in the hearts of patients with chronic chagasic cardiomyopathy. Intercellular adhesion molecule is expressed by endothelial cells of both chagasic and nonchagasic individuals, but E-selectin was detected only on vessels of hearts from chagasic patients who had chronic cardiomyopathy. Most of the lymphocytes in these lesions express lymphocyte function antigen-1 (LFA-1), CD44, and very late antigen-4, and a few display weak expression of LFA-3. We propose that the expression of these adhesion molecules and major histocompatibility complex antigens by endothelial cells, myocardial cells, and lymphoid cells in these lesions contribute to the pathogenesis of chronic chagasic cardiomyopathy.
Asunto(s)
Moléculas de Adhesión Celular/análisis , Cardiomiopatía Chagásica/inmunología , Antígenos HLA/análisis , Miocardio/inmunología , Adulto , Anciano , Cardiomiopatía Chagásica/patología , Enfermedad Crónica , Selectina E , Femenino , Antígenos HLA-DR/análisis , Humanos , Inmunohistoquímica , Molécula 1 de Adhesión Intercelular , Antígeno-1 Asociado a Función de Linfocito/análisis , Masculino , Persona de Mediana Edad , Miocardio/patologíaRESUMEN
The inflammatory infiltrates in the heart lesions of chronic chagasic cardiomyopathy are composed predominantly of small lymphocytes with admixed macrophages, plasma cells, and segmented leukocytes. The phenotypes of the lymphoid cells in these infiltrates of human Chagas' disease have not been previously detailed. We used a panel of monoclonal and polyclonal antibodies to immunohistochemically characterize the inflammatory cells in frozen and fixed cardiac tissues from autopsied patients with severe chronic chagasic cardiomyopathy. In all cases, the inflammatory lesions were dominated by CD8+ lymphocytes, many of which expressed granzyme A. A few macrophage-like cells that expressed tumor necrosis factor-alpha were observed in each case. Relatively few natural killer cells or B lymphocytes were found in the lesions. These findings in human chagasic lesions are compatible with concepts that involve cytolysis and fibrosis, and new experimental findings that emphasize potential roles for CD8+ T cells in Chagas' disease.