RESUMEN
Leishmania parasites have an oxidative and chemical defense mechanism called trypanothione system (T[SH]2), the most abundant thiol system in trypanosomatids. This system has a central role in processing pentavalent antimony and resistance has been related to a better capacity to metabolize it through the activation of T[SH]2 enzymatic cascade. A biochemical approach was applied to assess the effect of trivalent (SbIII) and pentavalent antimony (SbV) on Trypanothione Reductase (TR) activity of two Leishmania (Viannia) braziliensis clinical isolates, which were labeled as responder (R) and non-responder (NR) after patient treatment with Glucantime®. Both isolates were characterized based on in vitro susceptibility to SbIII and SbV and trypanothione reductase (TR) activity. SbIII and SbV discriminated susceptibility profiles in all parasite forms, since isolate NR had significantly higher EC50 values than isolate R. Differences were observed in TR activity between promastigotes, axenic amastigotes and intracellular amastigotes: R (0.439 ± 0.009, 0.103 ± 0.01 and 0.185 ± 0.01AU.min-1.µg of protein-1) and NR (1.083 ± 0.04, 0.914 ± 0.04 and 0.343 ± 0.04 AU. min-1.µg of protein-1), respectively. Incubation with SbIII and SbV using each form EC50 value caused a time-dependent differential effect on TR activity suggesting that oxidative defense is related to the antimony susceptibility phenotype. Data gathered here shows a biochemical approach able to discriminate two L. (V.) braziliensis clinical isolates measurements TR activity of promastigotes, axenic amastigotes and intracellular amastigotes.
Asunto(s)
Leishmania braziliensis , Leishmania , Antimonio/farmacología , Antimoniato de MegluminaRESUMEN
The clinical presentations of skin diseases produced by different pathogens, as American tegumentary leishmaniasis (ATL) and sporotrichosis can be similar and possibly influenced by the skin immune system (SIS). The aim of the study was to understand the underlying mechanisms of skin inflammation produced by different pathogens. We used immunohistochemistry to analyze 96 patients: a- localized cutaneous leishmaniasis (LCL-ATL); b- sporotrichoid cutaneous leishmaniasis (SCL-ATL); c-lymphocutaneous (LC-SP); d- fixed (F-SP) sporotrichosis. LCL-ATL and SCL-ATL had a significantly higher percentage of CD8, FasL and NOS2 than sporotrichosis. In contrast, LC-SP had a substantially higher percentage of CD4, BCl2 and neutrophils than ATL lesions. These results indicated some differences in the profile of the in situ immune response suggesting that SIS is a complex, adaptable system capable of different responses to intracellular or extracellular pathogens. However, regardless of the etiological agents, the inflammatory reaction and clinical manifestations can be similar. SCL-ATL and LC-SP presented similarities in both clinical presentation and in situ inflammatory profile (CD3, CD22, neutrophils, macrophages). The clinical presentation of ATL and sporotrichosis could be explained by a combination of factors both of the host SIS and the etiological agent. The unbalanced host parasite relationship could result in atypical manifestations of skin disease.
Asunto(s)
Leishmaniasis Cutánea/patología , Esporotricosis/patología , Adulto , Femenino , Humanos , Inflamación/patología , Leishmaniasis Cutánea/metabolismo , Masculino , Esporotricosis/metabolismoRESUMEN
Mucosal Leishmaniasis (ML) may occur in both nasal and oral mucosa. However, despite the impressive tissue destruction, little is known about the oral involvement. To compare some changes underlying inflammation in oral and nasal ML, we performed immunohistochemistry on mucosal tissue of 20 patients with ML (nasal [n = 12]; oral [n = 8] lesions) and 20 healthy donors using antibodies that recognize inflammatory markers (CD3, CD4, CD8, CD22, CD68, neutrophil elastase, CD1a, CLA, Ki67, Bcl-2, NOS2, CD62E, Fas and FasL). A significantly larger number of cells, mainly T cells and macrophages, were observed in lesions than in healthy tissue. In addition, high nitric oxide synthase 2 (NOS2) expression was associated with a reduced detection of parasites, highlighting the importance of NOS2 for parasite elimination. Oral lesions had higher numbers of neutrophils, parasites, proliferating cells and NOS2 than nasal lesions. These findings, together with the shorter duration of oral lesions and more intense symptoms, suggest a more recent inflammatory process. It could be explained by lesion-induced oral cavity changes that lead to eating difficulties and social stigma. In addition, the frequent poor tooth conservation and gingival inflammation tend to amplify tissue destruction and symptoms and may impair and confuse the correct diagnosis, thus delaying the onset of specific treatment.
Asunto(s)
Leishmaniasis/inmunología , Leishmaniasis/patología , Mucosa Bucal/inmunología , Mucosa Bucal/patología , Mucosa Nasal/inmunología , Mucosa Nasal/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Factores Inmunológicos/análisis , Inflamación/inmunología , Inflamación/patología , Macrófagos/inmunología , Masculino , Microscopía , Persona de Mediana Edad , Linfocitos T/inmunologíaRESUMEN
OBJECTIVE: To evaluate dizziness in patients receiving meglumine antimoniate for the treatment of mucosal leishmaniasis. MATERIALS AND METHODS: We retrospectively studied 127 patients treated at the Laboratory of Leishmaniasis Surveillance, Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, between 1 January 1989 and 31 December 2004. RESULTS: A low dose of meglumine antimoniate (5 mg/kg/day) was used in 86.6 per cent of patients; a dose of 10 mg/kg/day or higher was used in 13.4 per cent of patients. Dizziness was reported by 4.7 per cent of patients. The adjusted odds ratios were 7.37 for dizziness in female patients, 4.9 for dizziness in patients aged 60 years or older, and 7.77 for dizziness in the presence of elevated serum lipase. CONCLUSION: We suggest that dizziness may be a side effect of meglumine antimoniate, particularly in elderly individuals, in females and in patients with elevated serum lipase.
Asunto(s)
Antiprotozoarios/efectos adversos , Mareo/inducido químicamente , Leishmaniasis Mucocutánea/tratamiento farmacológico , Meglumina/efectos adversos , Compuestos Organometálicos/efectos adversos , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Antiprotozoarios/administración & dosificación , Brasil/epidemiología , Niño , Preescolar , Mareo/epidemiología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Leishmaniasis Mucocutánea/epidemiología , Lipasa/sangre , Masculino , Meglumina/administración & dosificación , Antimoniato de Meglumina , Persona de Mediana Edad , Oportunidad Relativa , Compuestos Organometálicos/administración & dosificación , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Adulto JovenRESUMEN
Skin inflammation plays an important role during the healing of American tegumentary leishmaniasis (ATL), the distribution of cells in active lesions may vary according to disease outcome and parasite antigens in ATL scars have already been shown. We evaluated by immunohistochemistry, 18 patients with 1- or 3-year-old scars and the corresponding active lesions and compared them with healthy skin. Small cell clusters in scars organized as in the active lesions spreaded over the fibrotic tissue were detected, as well as close to vessels and cutaneous glands, despite a reduction in the inflammatory process. Analysis of 1-year-old scar tissue showed reduction of NOS2, E-selectin, Ki67, Bcl-2 and Fas expression. However, similar percentages of lymphocytes and macrophages were detected when compared to active lesions. Only 3-year-old scars showed reduction of CD3(+), CD4(+) and CD8(+)T cells, in addition to reduced expression of NOS2, E-selectin, Ki67 and BCl-2. These results suggest that the pattern of cellularity of the inflammatory reaction observed in active lesions changes slowly even after clinical healing. Analysis of 3-year-old scars showed reduction of the inflammatory reaction as demonstrated by decrease in inflammatory cells and in the expression of cell-activity markers, suggesting that the host-parasite balance was only established after that period.
Asunto(s)
Cicatriz/patología , Inflamación/inmunología , Inflamación/patología , Leishmaniasis Cutánea/patología , Adolescente , Adulto , Anciano , Animales , Cicatriz/parasitología , Femenino , Humanos , Inmunidad Celular , Inmunohistoquímica , Leishmaniasis Cutánea/parasitología , Masculino , Microscopía , Persona de Mediana Edad , Factores de Tiempo , Adulto JovenRESUMEN
Analyses of MLEE, RAPD and LSSP-PCR were used to compare the panel of american tegumentary leishmaniasis (ATL) isolates obtained from lesions of patients with rare clinical manifestations of the disease and typical lesions. All of the 34 samples analyzed by MLEE demonstrated similar electromorphic profiles with Leishmania (Viannia) braziliensis reference strain. Through the RAPD analysis, nine genetic profiles (genotypes) were identified. LSSP-PCR corroborates the initial screening and phenetic analysis has grouped the isolates into two major clusters comprising the nine different genotypes. Prevalent genotype defined as LbmtDNAgen1 was detected in the largest number of isolates. There was no association between genotypes and clinical symptoms. However, two different genotypes could be identified in the initial (LbmtDNAGen9) and reactivated lesion (LbmtDNAGen3) of the same patient. Our results support the idea of a less pronounced genotypic diversity among L. (V.) braziliensis circulating in the State of Rio de Janeiro and demonstrate the useful application of these molecular markers in genetics variability studies.
Asunto(s)
Variación Genética , Leishmania braziliensis/clasificación , Leishmaniasis Cutánea/parasitología , Animales , Brasil , Análisis por Conglomerados , ADN Protozoario/análisis , Electroforesis/métodos , Enzimas/análisis , Femenino , Marcadores Genéticos , Genotipo , Humanos , Leishmania braziliensis/enzimología , Leishmania braziliensis/genética , Leishmaniasis Mucocutánea/parasitología , Masculino , Filogenia , Reacción en Cadena de la Polimerasa/métodos , Técnica del ADN Polimorfo Amplificado AleatorioRESUMEN
BACKGROUND: The study of American tegumentary leishmaniasis (ATL) lesions might contribute to the understanding of the dynamics of the infection. OBJECTIVES: To examine the cellular infiltrate of cutaneous ATL lesions and to compare these results with the detection of the parasites and clinical data. METHODS: Lesions of 19 patients with ATL were evaluated through immunohistochemical analysis. RESULTS: The lesions presented an inflammatory reaction mainly consisting of T cells and macrophages. Analysis of the expression of nitric oxide synthase type 2 (NOS2) showed that its intensity was directly correlated with the number of CD3+ T cells. We also observed an association between high NOS2 expression and low quantity of parasites, highlighting the importance of NOS2 in the elimination of parasites. CONCLUSIONS: The present results suggest that (i) the inflammatory process is intense in cutaneous ATL lesions and maintains a similar activity for several months; (ii) the dynamics of cell infiltration change during this period, with a gradual decrease in CD8+ T cells, probably correlated with a reduction in the parasite number; (iii) neutrophils may participate in the inflammatory process even during later stages of infection; (iv) the relative increase in the number of CD4+ T cells associated with the onset of fibrosis may suggest a participation of these cells in the control of the inflammatory process; and (v) late lesions with tendency for healing usually show focal inflammation. The study of healing lesions might contribute to the understanding of the late steps of the control of the inflammatory process in ATL lesions.
Asunto(s)
Inflamación/inmunología , Leishmaniasis Cutánea/inmunología , Adolescente , Adulto , Anciano , Animales , Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Femenino , Humanos , Inmunidad Celular , Técnicas para Inmunoenzimas , Inflamación/enzimología , Inflamación/parasitología , Células de Langerhans/inmunología , Leishmania braziliensis/aislamiento & purificación , Leishmaniasis Cutánea/enzimología , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/patología , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Subgrupos de Linfocitos T/inmunologíaRESUMEN
Diffuse cutaneous leishmaniasis (DCL) is characterised by multiple and progressive cutaneous lesions, resistance to chemotherapy and Leishmania-specific T-cell anergy. We report the first autochthonous DCL case and the first human infection with Leishmania amazonensis in Rio de Janeiro State, Brazil, where only L. braziliensis is considered to be the causative agent of cutaneous leishmaniasis. Leishmania amazonensis was identified by multilocus enzyme electrophoresis and PCR-RFLP. Our case was diagnosed as DCL according to clinical, parasitological, histopathological and immunological criteria. These observations indicate that L. amazonensis is increasing its geographical distribution in Brazil, accounting for unusual clinical presentations in new transmission areas.
Asunto(s)
Leishmaniasis Cutánea Difusa/epidemiología , Animales , Brasil/epidemiología , Niño , Humanos , Leishmania/aislamiento & purificación , Leishmaniasis Cutánea Difusa/diagnóstico , Leishmaniasis Cutánea Difusa/parasitología , MasculinoRESUMEN
Whole-cell and soluble extracts of Leishmania promastigotes have both been used as skin test antigens and have also been tested as vaccine candidates. However, the differences in antigenicity between soluble and particulate Leishmania fractions are not known. We evaluated in vitro responses of PBMC from 30 American tegumentary leishmaniasis (ATL) patients and seven noninfected donors to different antigen preparations from Leishmania promastigotes, namely Leishmania amazonensis and L. braziliensis whole-cell extracts, as well as soluble and particulate fractions of L. amazonensis. All Leishmania antigen preparations stimulated significantly higher proliferation and interferon (IFN)-gamma production (but not interleukin (IL)-10 production) in PBMC from the leishmaniasis patients than in cells from the control subjects. The L. braziliensis whole-cell extract stimulated significantly higher cell proliferation and IFN-gamma production than the L. amazonensis whole-cell extract in the group of patients but not in the control group. This result can be explained by the fact that the patients were infected with L. braziliensis. Again in the group of patients, the PBMC proliferative responses as well as the levels of IFN-gamma and IL-10 stimulated by L. amazonensis whole-cell extract were significantly greater than those elicited by the L. amazonensis soluble fraction but were not significantly different from those elicited by the L. amazonensis particulate fraction. We found a higher antigenicity of the particulate fraction as compared to the soluble fraction, what suggests that the antigens present in the particulate fraction account for most of the antigenicity of whole-cell Leishmania promastigote antigen extracts.
Asunto(s)
Antígenos de Protozoos/inmunología , Leishmania/inmunología , Leishmaniasis Cutánea/inmunología , Leucocitos Mononucleares/inmunología , Animales , División Celular/inmunología , Humanos , Interferón gamma/inmunología , Interleucina-10/inmunología , Leishmania/ultraestructura , Leishmania braziliensis/inmunología , Leishmania braziliensis/ultraestructura , Microscopía Electrónica , SolubilidadRESUMEN
A positive reaction to the leishmanin skin test (LST) indicates previous contact with Leishmania antigens and is a useful criterion for the diagnosis of cutaneous leishmaniasis. In leishmaniasis vaccine trials, selection of volunteers has always been based on skin testing. During 1999 we performed a randomized controlled study in order to evaluate the immunogenicity of the LST. Fifty-nine (29 male and 30 female) healthy volunteer undergraduate students from the Medical School of Volta Redonda, Rio de Janeiro State, Brazil, with no evidence of previous infection with Leishmania, were randomly assigned into 2 groups: 29 subjects received LST and 30 received a placebo (merthiolate-phosphate-buffered saline). All volunteers received LST 41 d after the first injection of LST or placebo. Blood samples were taken immediately before the applications of LST or placebo for the assessment of Leishmania antigen-induced proliferation and cytokine production in peripheral blood mononuclear cell cultures. A significant increase in proliferative responses to L. braziliensis (P < 0.005) and L. amazonensis (P = 0.01) antigens as well as in L. braziliensis antigen-induced interferon-gamma production (P < 0.01) followed the application of LST but not the administration of the placebo. A single LST application is therefore able to induce Leishmania-specific cell-mediated immune responses. This observation should be considered in human trials of candidate vaccines against leishmaniasis.
Asunto(s)
Antígenos de Protozoos/inmunología , Leishmaniasis Cutánea/inmunología , Adulto , Brasil , Método Doble Ciego , Femenino , Humanos , Leishmaniasis Cutánea/prevención & control , Masculino , Pruebas CutáneasRESUMEN
Two former patients treated for the cutaneous form of American tegumentary leishmaniasis were reviewed eight and 11 years, respectively, following clinical cure. We were able to isolate Leishmania parasites in a culture of material from the two scar biopsies, and in one of them the parasite was characterized as Leishmania (Viannia) braziliensis. In both cases, the histopathology revealed discreet hyperceratosis and a slight infiltrate of mononuclear cells surrounding and on the walls of the surface and deep dermal vessels. No amastigotes were seen on immunohistochemical or histopathologic examination. The Montenegro skin test result and the in vitro lymphoproliferative response to Leishmania antigen were positive, but no specific IgG and IgM antibodies were detected. Otorhinolaryngologic examination showed no macroscopic alteration in the mucosae. These findings are important for the evaluation and criteria of post-treatment cure.
Asunto(s)
Cicatriz/parasitología , Leishmania braziliensis/fisiología , Leishmaniasis Cutánea/patología , Adulto , Animales , Biopsia , Femenino , Estudios de Seguimiento , Humanos , Leishmania braziliensis/aislamiento & purificación , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/parasitología , Masculino , Meglumina/uso terapéuticoRESUMEN
As a means of assessing the usefulness of the Rhesus macaque (Macaca mulatta) as a nonhuman primate model for studying cutaneous leishmaniasis, monkeys were infected with Leishmania amazonensis. Variation in the level of susceptibility was found; however, animals inoculated with 10(8) promastigotes provided consistent results as indicated by an earlier onset and/or larger size of lesions. Three monkeys, which had recovered from skin lesions, were challenge-infected using the same parasite strain/dose; although these animals remained susceptible to homologous infection, lesion size was smaller and healed faster than in the initial infection. The immunologic features during infection were assessed. Levels of IgM and IgG antibodies to promastigote antigens rose during active infection and then declined; immunoblot analyses indicated that numerous leishmanial antigens (predominately >30 kDa) were recognized. Delayed type hypersensitivity (DTH) responses and proliferative responses (PBL) developed during active infection and/or rechallenge. Circulating peripheral T cell subpopulations varied throughout the course of infection. Initially (6-8 weeks p.i.), CD4+ T cells appear to predominate; subsequently (15-21 weeks p.i.), an increase in CD8+ T cells was observed. Pathologic analyses indicated that lesions contained amastigotes with a mononuclear infiltrate of macrophages, lymphocytes, and plasma cells, and formation of tuberculoid-type granulomas. As the progression and resolution of leishmanial infection in rhesus macaques are very similar to those observed in humans, this primate model could be employed for elucidating the mechanisms of protective immunity in cutaneous leishmaniasis.
Asunto(s)
Modelos Animales de Enfermedad , Leishmaniasis Cutánea/veterinaria , Macaca mulatta/parasitología , Animales , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos , Western Blotting , Susceptibilidad a Enfermedades , Femenino , Inmunidad Celular , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/patología , Activación de Linfocitos , Masculino , Piel/patologíaRESUMEN
Forty-three Brazilians were immunized against American tegumentary leishmaniasis using a vaccine made of whole antigens from killed promastigotes of five American dermotropic Leishmania strains. None of the immunized subjects had a positive reaction in the Montenegro skin test (leishmanin) before vaccination, and 74% developed positive reactions in the skin test after vaccination. The proliferative responses of peripheral blood mononuclear cells (PBMC) induced by antigens from dermotropic Leishmania species were significantly higher after vaccination than before vaccination. However, with antigens from L. chagasi (a causative agent of American visceral leishmaniasis), there was no significant difference between the proliferative responses obtained before and after vaccination. Interferon-gamma was detected in the supernatants of L. braziliensis antigen-stimulated PBMC cultures after vaccination (but not before vaccination). One year after vaccination, PBMC were obtained from eight of the immunized individuals and stimulated with L. braziliensis antigens in proliferative response assays. In all cases, the majority of the responding cells were CD8+ T cells, in contrast to the results of a group of patients with active lesions of tegumentary leishmaniasis, whose L. braziliensis-reactive cells were mainly of the CD4+ T cell phenotype.
Asunto(s)
Leishmania/inmunología , Leishmaniasis Cutánea/prevención & control , Vacunas Antiprotozoos/inmunología , Linfocitos T/inmunología , Adulto , Animales , Antígenos de Protozoos/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Citometría de Flujo , Humanos , Inmunidad Celular , Inmunofenotipificación , Interferón gamma/biosíntesis , Leishmaniasis Cutánea/inmunología , Activación de Linfocitos , Masculino , Vacunas Antiprotozoos/administración & dosificación , Pruebas Cutáneas , Especificidad de la Especie , VacunaciónRESUMEN
Fourteen patients suffering from American cutaneous leishmaniasis were studied. Assays of the lymphocyte proliferative response induced in vitro by Leishmania braziliensis antigens were performed. After 5 days in culture, L. braziliensis-stimulated blast T cells were harvested for CD4+ and CD8+ phenotype analysis. When results before and at the end of therapy were compared, leishmaniasis patients showed an increase in the percentage of CD8+ blast T cells and a decline in the proportion of CD4+ blast T cells in cultures. The levels of gamma interferon in T-cell culture supernatants showed a tendency to increase when the patients were cured. These results show a pattern of higher proportions of Leishmania-reactive CD8+ T cells and lower proportions of Leishmania-reactive CD4+ T cells after cure.
Asunto(s)
Linfocitos T CD4-Positivos/fisiología , Antígenos CD8/análisis , Leishmania braziliensis/inmunología , Leishmaniasis Cutánea/inmunología , Subgrupos de Linfocitos T/fisiología , Adulto , Animales , Relación CD4-CD8 , Células Cultivadas , Femenino , Humanos , Interferón gamma/biosíntesis , Masculino , Persona de Mediana EdadRESUMEN
The host response to infection appears to be regulated by specific patterns of local cytokine production. In the mouse, resistance to many pathogens including Leishmania is associated with a TH1 cytokine profile, IL-2 and IFN-gamma; whereas susceptibility to infection is associated with production of TH2 cytokines, IL-4, IL-5, and IL-10. To determine the cytokine patterns of the local immune response to Leishmania infection in humans, we used the polymerase chain reaction to compare cytokine mRNAs in biopsy specimens of American cutaneous leishmaniasis. In localized cutaneous leishmaniasis and the Montenegro delayed-type hypersensitivity reaction, type 1 cytokine mRNAs such as IL-2, IFN-gamma, and lymphotoxin were relatively predominant. In the chronic and destructive mucocutaneous form of leishmaniasis, there was a mixture of type 1 and type 2 cytokines, with a striking abundance of IL-4 mRNA in lesions. These results suggest that clinical course of infection with Leishmania braziliensis in man is associated with specific local patterns of cytokine production.
Asunto(s)
Citocinas/metabolismo , Leishmaniasis/etiología , Adolescente , Adulto , Anciano , Secuencia de Bases , Biopsia , Niño , Femenino , Humanos , Leishmaniasis/metabolismo , Leishmaniasis/patología , Leishmaniasis Cutánea/patología , Linfocinas/genética , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Piel/química , Piel/patologíaRESUMEN
A limiting dilution analysis (LDA) was utilized to estimate the frequency of L. braziliensis braziliensis reactive T cells (Lbb-T cells) in peripheral blood and in the lesions of patients with mild localized cutaneous leishmaniasis (LCL) or with severe mucosal leishmaniasis (MCL). The frequencies of Lbb-T cells in peripheral blood varied from 1:107300 to 1:3587 and were not significantly different in MCL and LCL patients. However, a significant difference was encountered (P less than 0.02) between the T cells frequencies in cutaneous (1:748 to 1:45) and mucosal lesions (1:152 to 1:13). A positive correlation was also observed between these frequencies and the magnitude of delayed-type hypersensitivity (DTH) (P less than 0.01) and the presence of fibrinoid necrosis and granulomatous reaction in the site of the lesions (P less than 0.05). The lack of correlation between the severity of disease (MCL or LCL) and the frequency of Lbb-T cells in peripheral blood gave no indications towards understanding the physiopathology of severe or mild disease. However, the correlation between high T cell frequencies in the site of the lesions, the magnitude of DTH, the fibrinoid necrosis and the severity of the disease (MCL lesions) points to the possibility that the presence of a strong T cell dependent cellular immune response in the site of the lesions may have a deleterious effect. However, a local well modulated T cell immune response might provide healing of the lesions.
Asunto(s)
Antígenos de Protozoos/inmunología , Leishmania braziliensis/inmunología , Leishmania/inmunología , Leishmaniasis Mucocutánea/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Animales , Femenino , Humanos , Recuento de Leucocitos , Activación de Linfocitos , Masculino , Persona de Mediana EdadRESUMEN
Limiting dilution analysis was used to estimate the frequency of Leishmania-specific T cells from the peripheral blood of 18 human cases of American Cutaneous Leishmaniasis (ACL). Sixteen patients had localized cutaneous leishmaniasis (LCL) and two were recovered LCL patients. In 10 patients with active disease and in two with healed lesions the Leishmania-specific T cell frequencies ranged from 1/10(5) to 1/10(3). In six patients no proliferation was detected after 21 days of cell culture. This finding points to very low precursor frequencies in the peripheral blood of these patients. A significant correlation was found between the two groups with low or high Leishmania-specific T cell frequencies and the lymphoproliferative responses to leishmanial antigens. The majority of the blast-like Leishmania-specific T cells showed a helper/inducer (CD4) phenotype.