The anti-IRBP IgG1 and IgG2a response does not correlate with susceptibility to experimental autoimmune uveitis

Susceptibility to experimental autoimmune uveitis (EAU) in inbred mice has been associated with a dominant Th1 response. Elevated anti-inter-photoreceptor retinoid-binding protein (anti-IRBP) IgG2a/IgG1 antibody ratios have been implicated as candidate markers to predict disease severity. In the present study, both the anti-IRBP antibody isotype and severity of EAU phenotypes were examined in 4 non-isogenic genetically selected mouse lines to determine if they can be used as general markers of disease. Mice between 8 and 12 weeks old selected for high (H III) or low (L III) antibody response and for maximum (AIR MAX) or minimum (AIR MIN) acute inflammatory reaction (AIR) were immunized with IRBP. Each experiment was performed with at least 5 mice per group. EAU was evaluated by histopathology 21 days after immunization and the minimal criterion was inflammatory cell infiltration of the ciliary body, choroid and retina. Serum IgG1- and IgG2a-specific antibodies were determined by ELISA. EAU was graded by histological examination of the enucleated eyes. The incidence of EAU was lower in AIR MIN mice whereas in the other strains approximately 40 percent of the animals developed the disease. Low responder animals did not produce anti-IRBP IgG2a antibodies or interferon-gamma. No correlation was observed between susceptibility to EAU and anti-IRBP isotype profiles. Susceptibility to EAU is related to the intrinsic capacity to mount higher inflammatory reactions and increased production of anti-IRBP IgG2a isotype is not necessarily a marker of this immunologic profile.

Comparação da secreção de citocinas (IL-4, IL-5, IL-6, IL-10) entre pacientes com nefropatia da IgA e deficiência de IgA / Comparison of the cytokine secretion (IL-4, IL-5, IL-6, IL-10) among patients with IgA nephropathy and IgA deficiency

Objetivo: A nefropatia primária da IgA (NIgA) e adeficiência de IgA (DIgA) constituem as formas maiscomuns de glomerulonefrite e de deficiência primáriade anticorpos, respectivamente, despertando interesseespecial o fato de ambas envolverem distúrbios contrastantes da produção da IgA. O objetivo deste trabalho foi comparar os níveis de citocinas possivelmente implicadas na produção da IgA (IL-4, IL-5, IL-6, IL-10) em pacientes com NIgA ou DIgA. Casuística e Métodos: Foram estudados 18 pacientes com NIgA (hematúria microscópica e proteinúria persistente ou intermitente e biópsia renal percutânea com depósito de IgA em mesângio glomerular detectado por imunofluorescência), sendo nove do gênero masculino e nove do feminino, com média de idade de 33,2 anos; 17 pacientes com DIgA (níveis séricos de IgA menores do que 7 mg/dL e níveis normais ou elevados de IgG e IgM), sendo 13 do gênero masculino e quatro do feminino, com média de idade de 25,5 anos; dez voluntários sadios (dois do gênero masculino e oito do feminino com média de idade de 30,7 anos). As citocinas foram quantificadas por método imunoenzimático em sobrenadante de cultura de PMBC após 48 horas de estímulo com fitohemaglutinina . Resultados: Foram observados: 1) níveis elevadosde IL-5 e de IL-10 e baixos de IL-6 em pacientes com NIgA em relação aos pacientes com DIgA e controlessadios; 2) níveis semelhantes de IL-4 em ambos gruposde pacientes e mais elevados na NIgA em comparaçãoaos controles sadios; 3) níveis similares de todasas citocinas testadas em pacientes com DIgA e controlessadios. Conclusões: Os níveis elevados de IL-5 encontrados na NIgA reforçam a importância desta citocina na síntese de IgA, cujos níveis séricos estão aumentados em aproximadamente 50 per cent dos casos; os níveis elevados de IL-4 e IL-5 encontrados nestes pacientes sugerem que estas duas citocinas possam estar envolvidas na glicosilação da IgA e seu conseqüente depósito em mesângio renal; os níveis elevados de IL-10 e baixos de IL-6 observados em pacientes com NIgA reforçam a hipótese de que a IL-10 esteja implicada na síntese da IgA em humanos e sugerem que esta citocina possa desempenhar um papel regulador sobre a produção deIL-6.

Alterações da imunidade celular associada à patogênese da imunodeficiência Comun variável / Changes in cellular immunity asssociated with the pathogenisis of common variable immunodeficiency

Objetivo: Avaliação da morte celular por ativação em linfócitos T de pacientes com imunodeficiência comum variável (CVID) e de outros parâmetros da resposta imune. Métodos: Células mononucleares obtidas a partir de sangue periférico (PBMC) de 32 pacientes com CVID e 32 indivíduos normais foram utilizadas para o estudo da expressão de CD40L, linfoproliferação e apoptose, Para a análise de marcadores de ativação (CD25 e CD69) e de interação entre células T e B (CD70) PBMC foram estimuladas por diferentes tempos (24, 48, 72 e 96 horas), Os sobrenadantes de cultura foram utilizados para quantificação de citocinas (IL-2, IL-4, IL-5 e IFN-y) por ELISA. Todos os testes laboratoriais foram aplicados no grupo controle de voluntários sadios. Os resultados foram analisados utilizando testes de diferença de proporções, ANOV A, Kruskal-Wallis e a prova de Mann-Whitney. Resultados: O grupo de pacientes com CVID demonstrou aumento percentual de linfócitos CD3/CD4 que sofreram apoptose em relação ao grupo controle (p< (Au) pacientes. destes anticorpos por mediada e celular resposta da prejuízo conseqüente com Th2, citocinas de diminuída síntese além CD70, CD69 CD25, CD40L, expressão circulantes, B T células nas decréscimo pelo responsável seja fenômeno este que sugere ativadas morte aumento O Conclusões: normais. indivíduos grupo o comparados quando CVID pacientes.

Lack of evidence for superantigen activity of Toxoplasma gondii towards human T cells

Toxoplasma gondii is an obligatory intracellular parasite whose life cycle may include man as an intermediate host. More than 500 million people are infected with this parasite worldwide. It has been previously reported that T. gondii contains a superantigen activity. The purpose of the present study was to determine if the putative superantigen activity of T. gondii would manifest towards human T cells. Peripheral blood mononuclear cells (PBMC) from individuals with no previous contact with the parasite were evaluated for proliferation as well as specific Vá expansion after exposure to Toxoplasma antigens. Likewise, PBMC from individuals with the congenital infection were evaluated for putative Vá family deletions in their T cell repertoire. We also evaluated, over a period of one year, the PBMC proliferation pattern in response to Toxoplasma antigens in patients with recently acquired infection. Some degree of proliferation in response to T. gondii was observed in the PBMC from individuals never exposed to the parasite, accompanied by specific Vá expansion, suggesting a superantigen effect. However, we found no specific deletion of Vá (or Valpha) families in the blood of congenitally infected individuals. Furthermore, PBMC from recently infected individuals followed up over a period of one year did not present a reduction of the Vá families that were originally expanded in response to the parasite antigens. Taken together, our data suggest that T. gondii does not have a strong superantigen activity on human T cells

Cytokine production profile of heart-infiltrating T cells in Chagas' disease cardiomyopathy

The hallmark of chronic Chagas'disease cardiomyopathy (CCC) is the finding of a T cell-rich inflammatory mononuclear cell infiltrate in the presence of extremely few parasites in the heart lesions. The scarcity of parasites in affected heart tissue casts doubt on the direct participation of Trypanosoma cruzi in CCC heart tissue lesions, and suggests the possible involvement of autoimmunity. The cells in the infiltrate are presumably the ultimate effectors of tissue damage, and there is evidence that such cells recognize cardiac myosin in molecular mimicry with T. cruzi proteins rather than primary reactivity to T. cruzi antigens (Cunha-Neto et al. (1996) Journal of Clinical Investigation, 98:1709-1712). recently, we have studied heart-infiltrating T cells at the functional levels. In this short review we summarize the studies about the role of cytokines in human and experimental T. cruzi infection, along with our data on heart-infiltrating T cells in human Chagas'cardiomyopathy. The bulk of evidence points to a significant production of IFN-gamma and TNF-alpha which may be linked to T. cruzi induced IL-12 production.

Differential modulatory effect of IL-5 on MHC class II expression by macrophages and B cells

The present study examines the effect of interleukin 5 on the expression of class II major histocompatibility complex (MHC) in macrophages and B cells. treatment of splenic adherent cells, a population that contains mostly macrophages and dendritic cells, with 100 U/ml of recombinant interleukin 5 resulted in a decrease of 10 to 30% in cell surface MHC class II expression by macrophages. The treatment had no effect on class I MHC expression, or on the mRNA synthesis as evaluated by tritiated-uridine incorporation. The same treatment of B cells resulted in the delineation of two groups with regard to class II MHC expression in a previously more homogeneous population. One group had an increase in surface Ia expression and the other had a decrease in the expression of this molecule. These results suggest that interleukin 5 has a role in MHC class II regulation

Prostaglandin E2 inhibits proliferation but not interleukin-2 production by phorbol ester plus calcium ionophore-activated murine T cell clones

We have investigated the effect of prostaglandin E2 (PGE2) on the T lymphocyte activation pathway. 2. At physiologically attainable concentrations (-0.1 micronM), PGE2 effectively inhibited the proliferation of murine antigen0specific "helper" T cell clones stimulated either with specific antigen in the presence of macrophages or with phorbol ester plus calcium ionophore A23187. The inhibition was not reversed by the addition of exogenous Interleukin 2(IL-2) in either case. 3. PGE treatment at the same concentrations did not inhibit IL-2 production by phorbol ester plus calcium ionophore-stimulated T cell clones as assayed by CTLL proliferation. 4. These results suggest that the major target (or targets) of PGE) inhibition directly on T cells lies in the IL-2 signal transduction pathway rather than in the early activation events leading to T cell activation