RESUMO
In human cutaneous leishmaniasis (CL), the immune response is mainly mediated by T-cells. The role of CD8+ T-lymphocytes, which are related to healing or deleterious functions, in affecting clinical outcome is controversial. The aim of this study was to evaluate T-cell receptor diversity in late-differentiated effector (LDE) and memory CD8+ T-cell subsets in order to create a profile of specific clones engaged in deleterious or protective CL immune responses. Healthy subjects, patients with active disease (PAD) and clinically cured patients were enrolled in the study. Total CD8+ T-lymphocytes showed a disturbance in the expression of the Vβ2, Vβ9, Vβ13.2, Vβ18 and Vβ23 families. The analyses of CD8+T-lymphocyte subsets showed high frequencies of LDE CD8+T-lymphocytes expressing Vβ12 and Vβ22 in PAD, as well as effector-memory CD8+ T-cells expressing Vβ22. We also observed low frequencies of effector and central-memory CD8+ T-cells expressing Vβ2 in PAD, which correlated with a greater lesion size. Particular Vβ expansions point to CD8+ T-cell clones that are selected during CL immune responses, suggesting that CD8+ T-lymphocytes expressing Vβ12 or Vβ22 are involved in a LDE response and that Vβ2 contractions in memory CD8+T-cells are associated with larger lesions.
.Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , /imunologia , Leishmaniose Cutânea/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Subpopulações de Linfócitos T/imunologia , Brasil , Ativação Linfocitária/imunologia , Receptores de Antígenos de Linfócitos T/análiseRESUMO
In human cutaneous leishmaniasis (CL), the immune response is mainly mediated by T-cells. The role of CD8+ T-lymphocytes, which are related to healing or deleterious functions, in affecting clinical outcome is controversial. The aim of this study was to evaluate T-cell receptor diversity in late-differentiated effector (LDE) and memory CD8+ T-cell subsets in order to create a profile of specific clones engaged in deleterious or protective CL immune responses. Healthy subjects, patients with active disease (PAD) and clinically cured patients were enrolled in the study. Total CD8+ T-lymphocytes showed a disturbance in the expression of the Vß2, Vß9, Vß13.2, Vß18 and Vß23 families. The analyses of CD8+T-lymphocyte subsets showed high frequencies of LDE CD8+T-lymphocytes expressing Vß12 and Vß22 in PAD, as well as effector-memory CD8+ T-cells expressing Vß22. We also observed low frequencies of effector and central-memory CD8+ T-cells expressing Vß2 in PAD, which correlated with a greater lesion size. Particular Vß expansions point to CD8+ T-cell clones that are selected during CL immune responses, suggesting that CD8+ T-lymphocytes expressing Vß12 or Vß22 are involved in a LDE response and that Vß2 contractions in memory CD8+T-cells are associated with larger lesions.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Leishmaniose Cutânea/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Brasil , Feminino , Humanos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T/análise , Adulto JovemRESUMO
O vírus linfotrópico das células T humanas do tipo 1 (HTLV-1) é o agente etiológico da mielopatia associada ao HTLV / paraparesia espástica tropical (HAM / TSP ), que ocorre em menos de 5 % dos indivíduos infectados. A resposta imune controla parcialmente a infecção, porém pode estar ligada a patogênese da doença. O objetivo deste estudo foi caracterizar fenotipicamente as subpopulações de linfócitos T, em pacientes assintomáticos e com diagnóstico de HAM/TSP. Foram avaliados 103 pacientes acompanhados no Centro de HTLV da Escola Bahiana de Medicina e Saúde Pública (EBMSP) e 19 controles não infectados. Os pacientes foram categorizados de acordo com o grau de certeza do diagnóstico de HAM/TSP: possível (Ps), provável (Pb) e definido (D), além de pacientes assintomáticos (ASS). O perfil fenotípico (CD25, CD45RA, CD45RO, HLA-DR, CD25, CCR-7, CD62L)...
The human T-cell lymphotropic vírus type 1(HTLV-1) is the etiological agent of HTLV- associated myelopathy/ Tropical spastic paraparesis(HAM/TSP), wich occurs in less then 5% of the infected individuals. The immune response partially controls the infection, but may be linked to the pathogenesis of disease. The aim of this study was to characterize phenotipically T lymphocyte subpopulations in asymptomatic and in patients diagnosed with HAM/TSP. We evaluated 103 patients treated at the center for HTLV of Bahia School of Medicine and Public Health (EBMSP) and 19 uninfected controls. Patients were categorized as asymptomatic and according to the degree of certainty of the diagnosis of HAM/TSP: Possible(Ps), Probable(Pb) and Definite(D). The phenotypic profile (CD25, CD45RA, CD45RO, HLA-DR, CCR-7, CD62L)...
Assuntos
Humanos , Doenças da Medula Espinal/diagnóstico , Doenças da Medula Espinal/imunologia , Doenças da Medula Espinal/patologia , Doenças da Medula Espinal/prevenção & controle , Doenças da Medula Espinal/virologia , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos de Linfócitos T/administração & dosagem , Receptores de Antígenos de Linfócitos T/análise , Receptores de Antígenos de Linfócitos T/imunologia , Vírus Linfotrópico T Tipo 1 Humano/patogenicidadeRESUMO
The role of non-lymphoid tissue T cells expressing the BV9 family T-cell receptor (TCRBV9) was studied in mice chronically infected with the Trypanosoma cruzi. Heart and skeletal muscles had higher frequencies and ratios of CD8+ TCRBV9+ to CD4+ TCRBV9+ T cells than lymph nodes. Also, homing experiments of CFSE-labeled T cells showed preferential homing of TCRBV9+ T cells to heart tissue. In vitro proliferation assays showed higher [3H]thymidine uptake by non-lymphoid tissue TCRBV9+ T cells than lymph node TCRBV9+ T cells co-cultured with antigen-presenting cells (APC), in response to T. cruzi amastigote antigens (TcAg). Lymph node TCRBV9+ T cells secreted IFN-gamma and IL-10, but not IL-4, upon stimulation with TcAg in the presence of APC. Moreover, non-lymphoid tissue-derived TCRBV9+ T cells showed impairment of IFN-gamma, no IL-4 production, and higher levels of IL-10 secretion under the same conditions. Our results show that T. cruzi-specific IFN-gamma- and IL-10-producing TCR BV9+ T cells develop in the mouse lymph nodes during chronic infection with T. cruzi. Upon homing to non-lymphoid parasitized tissues, IFN-gamma secretion might subside due to the overt secretion of IL-10, of which TCRBV9+ T cells represent a significant source.
Assuntos
Interferon gama/metabolismo , Interleucina-10/imunologia , Receptores de Antígenos de Linfócitos T/análise , Linfócitos T/imunologia , Trypanosoma cruzi/imunologia , Animais , Proliferação de Células , Doença de Chagas/imunologia , Interleucina-4/metabolismo , Linfonodos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Músculo Esquelético/imunologia , Miocárdio/imunologia , Linfócitos T/químicaRESUMO
Evidence indicates that human T-cell lymphotropic virus type 1 (HTLV-1) infection leads to chronic immunosuppression and a greater susceptibility to infectious diseases. Spontaneous in vitro proliferation of peripheral blood mononuclear cells (PBMC) is an important immunological feature of HTLV-1-infected individuals. However, the association between spontaneous proliferation and immunosuppression is not clear. In this study, we evaluated the cellular immune responses of PBMC from 58 asymptomatic HTLV-1-infected individuals with PBMC showing or not showing spontaneous proliferation. Individuals with PBMC that spontaneously proliferated had increased proportions of CD4 T cells expressing CD45RO and dramatically reduced responses to recall antigens. In addition, frequencies of positive responses to recall antigens were also decreased in HTLV-infected individuals without spontaneous proliferation of PBMC. There was a polyclonal expansion of multiple T-cell receptor Vbeta families of CD4+ T lymphocytes in patients with spontaneous proliferation. We observed that HTLV-1 induced an immunosuppression characterized by a decrease in the stimulation index to a recall antigen, even in individuals who did not present spontaneous proliferation. On the other hand, only patients with PBMC presenting spontaneous proliferation showed polyclonal activation and increased proportion of CD4 T cells expressing CD45RO.
Assuntos
Antígenos/imunologia , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Tolerância Imunológica/imunologia , Leucócitos Mononucleares/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Proliferação de Células , Feminino , Humanos , Memória Imunológica , Antígenos Comuns de Leucócito/biossíntese , Leucócitos Mononucleares/citologia , Ativação Linfocitária , Masculino , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Receptores de Antígenos de Linfócitos T/análise , Receptores de Antígenos de Linfócitos T/biossínteseRESUMO
Nasal NK/T-cell lymphoma is a unique form of lymphoma highly associated with Epstein-Barr virus, and with a characteristic geographic distribution. Recently, we showed that p53 is overexpressed in a high percentage of nasal NK/T-cell lymphomas. The aim of this study was to analyze the status of the p53 gene, and correlate it with the expression of p53 protein and its downstream target, the cyclin-dependent kinase inhibitor p21, in a series of 25 cases of well-characterized nasal NK/T-cell lymphoma from Mexico. The highly conserved exons 5 to 8 of the p53 gene were amplified by polymerase chain reaction and screened for mutations by denaturing high-pressure liquid chromatography. Abnormal polymerase chain reaction products detected by denaturing high-pressure liquid chromatography and additional selected cases were sequenced. In addition, the incidence of loss of heterozygosity at the p53 locus was analyzed in 12 cases. Of the 25 patients, 17 were male and 8 female (M:F ratio, 2.1:1), with a median age of 43 years (range, 21 to 93 years). Morphologically, most of the cases were composed of a mixture of medium-sized cells and large transformed cells (21 cases), and four cases were composed exclusively of large transformed cells. Three different groups determined by p53 gene status and expression of p53 protein were identified: group 1 was p53 +/p53 mutated (five cases, all with p53 missense mutations). Morphologically, three of the five cases were composed of large cells. All five cases revealed overexpression of p53 in the majority of the tumor cells with a mean of 86%. Unexpectedly, three of these cases also showed overexpression of p21. Four of the five patients presented with clinical stage IVB and died with disease. Group 2 was p53+/p53 wild-type (10 cases). Histologically, nine cases were of the mixed type, and one of the large cell type. The percentage of p53 overexpressing cells was lower than in the previous group with a mean of 23%. p21 was positive in 7 of the 10 cases. Six patients in this group presented with clinical stages I to II and four patients with advanced disease (stage III and IV). Five patients are alive 12 to 120 months later (mean, 24 months), three with no evidence of disease. Group 3 was p53-/p53 wild-type (10 cases). All cases showed mixed cell morphology. p21 was positive in 5 of 10 cases. Four patients presented with clinical stage I to II and six patients with advanced disease. Four patients are alive with no evidence of disease 9 to 60 months later (mean, 10 months). Overall, p53 mutations were present in 24% (5 of 21) of the evaluable cases, all of them overexpressing p53 in the majority of tumor cells. Cases with p53 mutations were associated with large cell morphology (P = 0.0162) and presented more often with advanced stage disease. Loss of heterozygosity at chromosome 17p was found only in 2 of the 12 (17%) cases investigated, both cases showed p53 mutations of the remaining allele. P21 overexpression (60% of cases) is frequent in nasal NK/T-cell lymphoma and seems to be independent of p53 gene status. The overexpression of p53 and p21, independent of p53 mutations, although as yet not clear, might be the result of Epstein-Barr virus infection, and warrants further investigation.
Assuntos
Complexo CD3 , Células Matadoras Naturais/patologia , Linfoma de Células T/patologia , Neoplasias Nasais/patologia , Proteínas , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Antígeno CD56/análise , Cromossomos Humanos Par 17/genética , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/genética , Análise Mutacional de DNA , DNA de Neoplasias/química , DNA de Neoplasias/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Células Matadoras Naturais/química , Perda de Heterozigosidade , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Linfoma de Células T/genética , Linfoma de Células T/metabolismo , Masculino , Proteínas de Membrana/análise , México , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Neoplasias Nasais/genética , Neoplasias Nasais/metabolismo , Proteínas de Ligação a Poli(A) , Proteínas de Ligação a RNA/análise , Receptores de Antígenos de Linfócitos T/análise , Antígeno-1 Intracelular de Células TRESUMO
In previous work we have demonstrated that spleen mononuclear (Spm) cells from rats obtained 14 days after infection with Cryptococcus neoformans showed a diminution in proliferative response to Concanavalin A (Con A). In this study we further investigate some characteristics of the Spm cell population involved in the immunosuppressor phenomenon induced by C. neoformans. We observed that unstimulated Spm cells expressing T-cell receptor (TCR+) from infected rats were reduced in number after 96 h of culture. When the Spm cells from infected rats were stimulated with Con A, increased production of IL-10, reduced levels of IL-2, and decreased CD11a surface expression were shown. These immunosuppressor phenomena were also observed when the capsular polysaccharide, glucuronoxylomannan (GXM), was added to cultures of Spm cells from normal rats. However, GXM had a more pronounced effect in reducing the number of cells surviving in culture than that observed during infection and produced an increase in IL-4 production by Con-A-stimulated Spm cells. Addition of anti-IL-10 monoclonal antibody to cultures restored the lymphoproliferation of Spm cells from infected animals, indicating that IL-10 production is a suppressor mechanism of cell-mediated immunity during experimental infection. The results presented here indicate that at least two mechanisms mediate the nonspecific suppression in this model of cryptococcosis: IL-10 production and diminution of the number of T cells. GXM could be involved, since it has a pronounced effect in the reduction of Spm cells in vitro.
Assuntos
Criptococose/imunologia , Cryptococcus neoformans/fisiologia , Interleucina-10/biossíntese , Linfopenia/etiologia , Polissacarídeos/fisiologia , Animais , Concanavalina A/farmacologia , Criptococose/complicações , Cryptococcus neoformans/química , Feminino , Imunidade Celular , Interleucinas/biossíntese , Ativação Linfocitária/efeitos dos fármacos , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Polissacarídeos/farmacologia , Ratos , Ratos Wistar , Receptores de Antígenos de Linfócitos T/análise , Baço/imunologiaRESUMO
Th2 type lymphocytes are characterized by high expression of CD30 glycoprotein. Increased serum levels of CD30 and Th2 IL-4 producing T-cells are found during AIDS progression. Since HIV-positive patients are more susceptible to periodontal disease, quantitative analysis of positive cells for the CD30 receptor in chronic gingivitis of both HIV-infected and non-infected patients (NSG) would help to clarify the immunoregulation of HIV-associated periodontal diseases. The purpose of this study was to evaluate CD30+ lymphocytes in gingival biopsies from sites exhibiting chronic gingivitis on HIV-positive patients (CG-HIV) and NSG. A biotin-streptavidin amplified system was used for identification of the CD30 receptor. The results demonstrated increased proportions of Th2 cells in CG-HIV as compared to NSG. Additional studies are necessary to understand the importance of these cells to the biological activity or inactivity of the disease.
Assuntos
Gengivite/imunologia , Soropositividade para HIV/imunologia , Antígeno Ki-1/análise , Células Th1/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Adulto , Biópsia , Biotina , Ligante CD30 , Estudos de Casos e Controles , Doença Crônica , Progressão da Doença , Suscetibilidade a Doenças , Feminino , Soronegatividade para HIV/imunologia , Humanos , Indicadores e Reagentes , Interleucina-4/sangue , Antígeno Ki-1/sangue , Ligantes , Contagem de Linfócitos , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Projetos Piloto , Receptores de Antígenos de Linfócitos T/análise , Estreptavidina , Linfócitos T/imunologiaRESUMO
Bone marrow transplantation is an accepted therapy for hematologic malignancies, aplastic anemia, metabolic disorders, and solid tumors. However, graft-versus-host disease (GVHD) and failure of engraftment have limited the widespread application of this technology to nonmalignant disease states. The use of purified bone marrow stem cells has been suggested as an approach to promote engraftment yet avoid GVHD. Although bone marrow stem cells, purified by cell sorting, engraft and repopulate lethally irradiated genetically identical recipients, they do not engraft in major histocompatibility complex (MHC)-disparate allogeneic recipients. We report for the first time the characterization of a novel cell population of donor bone marrow origin, separate from the hematopoietic stem cell, that facilitates engraftment of purified allogeneic bone marrow stem cells in an MHC-specific fashion without causing GVHD. Although 1,000 purified stem cells (c-kit+/Sca-1+/lineage-) reliably repopulate syngeneic mouse recipients, 10 times that number do not engraft in MHC-disparate allogeneic recipients. The addition of as few as 30,000 facilitating cells (CD8+/CD45R+/TCR-) is sufficient to permit engraftment of purified stem cells in MHC-disparate recipients. The cell surface phenotype of this purified cellular population differs significantly from other characterized lineages of lymphoid or myeloid origin. Based on multiparameter rare-events cell sorting, the facilitating fraction is CD8+, CD3+, CD45R+, Thy 1+, class IIdim/intermediate but alpha beta-TCR- and gamma delta-TCR-. This cellular population comprises approximately 0.4% of the total bone marrow and is separate from the hematopoietic stem cell. The coadministration of purified facilitating cells plus stem cells to optimize engraftment yet avoid GVHD may expand the potential application of bone marrow transplantation to disease states in which the morbidity and mortality associated with conventional BMT cannot be justified.
Assuntos
Células da Medula Óssea , Transplante de Medula Óssea , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/imunologia , Imunofenotipagem , Animais , Medula Óssea/fisiologia , Complexo CD3/análise , Antígenos CD8/análise , Separação Celular , Citometria de Fluxo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/fisiologia , Antígenos de Histocompatibilidade Classe II/análise , Antígenos Comuns de Leucócito/análise , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microscopia Eletrônica , Receptores de Antígenos de Linfócitos T/análise , Antígenos Thy-1/análiseRESUMO
The mechanisms by which Trypanosoma cruzi causes dysfunction in normal human lymphocytes was studied by using an in vitro system in which purified parasites and normal peripheral blood mononuclear cells are co-cultured in the presence or absence of mitogens. Our results have shown that T. cruzi impairs the expression of receptors for interleukin-2 (IL-2R) and transferrin, activated lymphocyte membrane molecules which play key roles in controlling progression through the cell cycle. T. cruzi also downregulates the expression of constitutive lymphocyte molecules (e.g., CD4, and CD8) involved in the interactions between antigen-presenting cells and T lymphocytes as well as the expression of T cell receptor (TCR) and CD3 molecules. The latter molecular structures are physically associated and are responsible for signaling and transducing activation events resulting from antigen binding. Stimulated B lymphocytes also display reduced IL-2R expression in the presence of T. cruzi. In contrast, neither the expression of EA-1 molecules by T lymphocytes nor that of CD19 and CD20 molecules by B lymphocytes is affected by this parasite. Thus, the T. cruzi effects are selective, not indiscriminate. The activated T cell populations affected by T. cruzi show concomitant reductions in the levels of expression of IL-2R and CD4, IL-2R and CD8, IL-2R and CD3 or IL-2R and TCR as well as in their capacity to proliferate; 3H-thymidine uptake decreases and there is a massive arrest of cells at the G0/G1a phase of the cell cycle. The immunosuppressive effects of T. cruzi are reproduced by a protein molecule(s) released spontaneously by the parasite termed TIF (for trypanosomal immunosuppressive factor). We report herein that TIF does not compete with IL-2 for binding to IL-2R and that shedding of IL-2R is decreased in the presence of T. cruzi. Moreover, the intracellular level of IL-2R was found to be lower than that found in control cells cultured in the absence of parasites. These results suggest that suppressed IL-2R reflects a modification induced by T. cruzi at a time coinciding with or preceding IL-2R mRNA translation. Studies are underway to identify the earliest process targeted by T. cruzi.
Assuntos
Antígenos de Protozoários/imunologia , Tolerância Imunológica/imunologia , Ativação Linfocitária/imunologia , Linfócitos/imunologia , Fatores Supressores Imunológicos/imunologia , Trypanosoma cruzi/imunologia , Animais , Antígenos CD/análise , Linfócitos B/imunologia , Ciclo Celular/imunologia , Células Cultivadas , Humanos , Camundongos , Receptores de Antígenos de Linfócitos T/análise , Receptores de Interleucina-2/análise , Linfócitos T/imunologiaRESUMO
The mechanisms by which Trypanosoma cruzi causes dysfunction in normal human lymphocytes was studied by using an in vitro system in which purified parasites and normal peripheral blood mononuclear cells are co-cultured in the presence or absence of mitogens. Our results have shown that T. cruzi impairs the expression of receptors for interleukin-2 (IL-2R) and transferrin, activated lymphocyte membrane molecules which play key roles in controlling progression through the cell cycle. T. cruzi also downregulates the expression of constitutive lymphocyte molecules (e.g., CD4, and CD8) involved in the interactions between antigen-presenting cells and T lymphocytes as well as the expression of T cell receptor (TCR) and CD3 molecules. The latter molecular structures are physically associated and are responsible for signaling and transducing activation events resulting from antigen binding. Stimulated B lymphocytes also display reduced IL-2R expression in the presence of T. cruzi. In contrast, neither the expression of EA-1 molecules by T lymphocytes nor that of CD19 and CD20 molecules by B lymphocytes is affected by this parasite. Thus, the T. cruzi effects are selective, not indiscriminate. The activated T cell populations affected by T. cruzi show concomitant reductions in the levels of expression of IL-2R and CD4, IL-2R and CD8, IL-2R and CD3 or IL-2R and TCR as well as in their capacity to proliferate; 3H-thymidine uptake decreases and there is a massive arrest of cells at the G0/G1a phase of the cell cycle. The immunosuppressive effects of T. cruzi are reproduced by a protein molecule(s) released spontaneously by the parasite termed TIF (for trypanosomal immunosuppressive factor). We report herein that TIF does not compete with IL-2 for binding to IL-2R and that shedding of IL-2R is decreased in the presence of T. cruzi. Moreover, the intracellular level of IL-2R was found to be lower than that found in control cells cultured in the absence of parasites. These results suggest that suppressed IL-2R reflects a modification induced by T. cruzi at a time coinciding with or preceding IL-2R mRNA translation. Studies are underway to identify the earliest process targeted by T. cruzi
Assuntos
Animais , Humanos , Camundongos , Antígenos de Protozoários/imunologia , Tolerância Imunológica/imunologia , Ativação Linfocitária/imunologia , Linfócitos/imunologia , Fatores Supressores Imunológicos/imunologia , Trypanosoma cruzi/imunologia , Antígenos CD/análise , Linfócitos B/imunologia , Ciclo Celular/imunologia , Células Cultivadas , Receptores de Antígenos de Linfócitos T/análise , Receptores de Interleucina-2/análise , Linfócitos T/imunologiaRESUMO
While studying the alpha beta T cell receptor repertoire in rheumatoid arthritis (RA) patients, we found that the frequency of V beta 14+ T cells was significantly higher in the synovial fluid of affected joints than in the peripheral blood. In fact, V beta 14+ T cells were virtually undetectable in the peripheral blood of a majority of these RA patients. beta-chain sequences indicated that one or a few clones dominated the V beta 14+ population in the synovial fluid of individual RA patients, whereas oligoclonality was less marked for other V beta's and for V beta 14 in other types of inflammatory arthritis. These results implicate V beta 14-bearing T cells in the pathology of RA. They also suggest that the etiology of RA may involve initial activation of V beta 14+ T cells by a V beta 14-specific superantigen with subsequent recruitment of a few activated autoreactive v beta 14+ T cell clones to the joints while the majority of other V beta 14+ T cells disappear.
Assuntos
Artrite Reumatoide/imunologia , Antígenos HLA-D/análise , Receptores de Antígenos de Linfócitos T/análise , Linfócitos T/imunologia , Sequência de Aminoácidos , Artrite/imunologia , Artrite Reumatoide/sangue , Humanos , Substâncias Macromoleculares , Dados de Sequência Molecular , Líquido Sinovial/imunologiaRESUMO
Recently, there have been a number of reports that gamma delta T cells are stimulated by heat shock, or stress, proteins. Although some alpha beta T cells are capable of recognizing heat shock proteins, we speculate that most or a group of gamma delta cells generally recognize this type of antigen. Recognition of heat shock proteins would enable gamma delta cells to respond to autologous tissue, and perhaps thus eliminate those cells that exhibit signs of stress, due for example to intracellular infection or transformation.
Assuntos
Proteínas de Choque Térmico/imunologia , Receptores de Antígenos de Linfócitos T/análise , Linfócitos T/fisiologia , Animais , Humanos , Receptores de Antígenos de Linfócitos T gama-deltaRESUMO
Thirty-one pediatric patients with acute renal allograft rejection were treated with the monoclonal antibody OKT3. In 24 cases, increased doses of steroids followed by a polyclonal antithymocyte globulin were ineffective in reversing the rejection episode. Twenty-eight patients completed the prescribed minimum 10-day treatment course, with effective rejection reversal in 22. Three patients failed to complete the course of therapy: one because of leukopenia that developed after the first dose, one because of a clotted graft, and another because of symptomatic cytomegalovirus infection. The overall success rate of OKT3 for rejection reversal was 74%; however, 55% of recipients had rebound rejection, and 85% of patients had detectable anti-OKT3 antibodies after completion of the course of therapy. Ten patients were treated with a second course of OKT3, and in eight of these patients, rejection was at least temporarily reversed. The starting dose of OKT3 for second-course therapy was the same as that used during first-course therapy, but in five cases the dose was increased during the course because of inadequate therapeutic response. Seven of these patients lost their grafts a mean of 6.5 months after completion of second-course therapy. We looked for anti-OKT3 antibody in nine recipients after completion of a second treatment course and found it in all nine. Our observations regarding a second treatment course with this monoclonal antibody preparation suggest that although rejection reversal may be observed, ultimate graft survival is poor and anti-OKT3 antibody formation is enhanced.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Rejeição de Enxerto/imunologia , Transplante de Rim/imunologia , Acetaminofen/uso terapêutico , Adolescente , Anticorpos Anti-Idiotípicos/análise , Anticorpos Monoclonais/administração & dosagem , Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos T/análise , Soro Antilinfocitário/uso terapêutico , Azatioprina/uso terapêutico , Complexo CD3 , Criança , Pré-Escolar , Difenidramina/uso terapêutico , Humanos , Imunoglobulina A , Lactente , Metilprednisolona/uso terapêutico , Prednisona/uso terapêutico , Receptores de Antígenos de Linfócitos T/análise , Recidiva , Linfócitos T/imunologiaRESUMO
Lymphocyte subsets and K-cell activity were evaluated in the peripheral blood of 21 patients with iron deficiency anemia. The results showed that the mean number of total lymphocytes, CD3 and CD4 subsets, and B lymphocytes were decreased in these patients. The K-cell activity as measured by specific cytotoxicity and cytotoxic capacity was decreased. However, studies performed in 16 of these patients after the treatment revealed the recovery of these parameters except the decreased K-cell activity. These findings demonstrate immunological abnormalities in iron deficiency anemia which could increase the susceptibility to infections.
Assuntos
Anemia Hipocrômica/imunologia , Células Matadoras Naturais , Subpopulações de Linfócitos , Adolescente , Adulto , Idoso , Citotoxicidade Celular Dependente de Anticorpos , Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos T/análise , Linfócitos B/patologia , Complexo CD3 , Antígenos CD4/análise , Antígenos CD8 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T/análiseRESUMO
The staphylococcal toxins are responsible for a number of diseases in man and other animals. Many of them have also long been known to be powerful T cell stimulants. They do not, however, stimulate all T cells. On the contrary, each toxin reacts with human T cells bearing particular V beta sequences as part of their receptors for major histocompatibility complex protein-associated antigen. The specificity of these toxins for V beta s puts them in the recently described class of superantigens and may account for the differential sensitivity of different individuals to the toxic effects of these proteins.
Assuntos
Toxinas Bacterianas/farmacologia , Receptores de Antígenos de Linfócitos T/imunologia , Staphylococcus , Linfócitos T/imunologia , Anticorpos , Antígenos de Diferenciação de Linfócitos T/análise , Toxinas Bacterianas/imunologia , Complexo CD3 , Antígenos CD8 , Antígenos HLA/análise , Humanos , Imunoensaio , Ativação Linfocitária , Receptores de Antígenos de Linfócitos T/análiseRESUMO
En un modelo experimental de inmunodeficiencia provocada por déficit de proteínas, se demuestra: 1) en el timo, existencia de graves alteraciones en sus poblaciones celulares que se encuentran drmáticamente disminuídas: W3/13+ (pan- T), W3/25+ (CD4+) y OX8+ (DC8+), existiendo una población celular que contiene TdT como único marcador; 2) alteraciones en el ciclo celular de la IgA que permitieron demostrar in vivo la presencia de células pre-B en placas de Peyer con alteración marcada en las subpoblaciones T; 3) los mecanismos involucrados en la inmunidad mediada por células son dañados por el déficit de proteínas y continúan alterados después de que dicho déficit ha sido superado; 4) en el timo, la administración por via oral de una dieta de caseína al 20% restaura la población celular- T W3/13+ luego de 21 días, pero la subpoblación W3/25+ (CD4+) se encuentra muy disminuida; 5) al mismo tiempo se reinicia, en placas de Peyer, la diferenciación de los precursores de células plasmáticas de clase IgA, aunque se encuentra la diferenciación de los precursores de células plamáticas de clase IgA, aunque se encuentra alterado, tanto en ellas como en ganglio mesentérico, el número absoluto de células que expresan y contienen IgA, así como el de las células T maduras, especialmente la población CD4+; 6) el dearrollo de un mecanismo de tolerancia a dextrina que es antígeno-específico, está mediado por células-T y puede ser transferido a receptores normales, ya sea con células provenientes de...
Assuntos
Ratos , Animais , Deficiência de Proteína/complicações , Nódulos Linfáticos Agregados/patologia , Timo/patologia , Antígenos de Diferenciação de Linfócitos T/análise , Imunidade Celular , Imunoglobulina A/análise , Ratos Endogâmicos , Receptores de Antígenos de Linfócitos T/análise , Receptores Virais/análiseRESUMO
En un modelo experimental de inmunodeficiencia provocada por déficit de proteínas, se demuestra: 1) en el timo, existencia de graves alteraciones en sus poblaciones celulares que se encuentran drmáticamente disminuídas: W3/13+ (pan- T), W3/25+ (CD4+) y OX8+ (DC8+), existiendo una población celular que contiene TdT como único marcador; 2) alteraciones en el ciclo celular de la IgA que permitieron demostrar in vivo la presencia de células pre-B en placas de Peyer con alteración marcada en las subpoblaciones T; 3) los mecanismos involucrados en la inmunidad mediada por células son dañados por el déficit de proteínas y continúan alterados después de que dicho déficit ha sido superado; 4) en el timo, la administración por via oral de una dieta de caseína al 20% restaura la población celular- T W3/13+ luego de 21 días, pero la subpoblación W3/25+ (CD4+) se encuentra muy disminuida; 5) al mismo tiempo se reinicia, en placas de Peyer, la diferenciación de los precursores de células plasmáticas de clase IgA, aunque se encuentra la diferenciación de los precursores de células plamáticas de clase IgA, aunque se encuentra alterado, tanto en ellas como en ganglio mesentérico, el número absoluto de células que expresan y contienen IgA, así como el de las células T maduras, especialmente la población CD4+; 6) el dearrollo de un mecanismo de tolerancia a dextrina que es antígeno-específico, está mediado por células-T y puede ser transferido a receptores normales, ya sea con células provenientes de... (AU)