RESUMO
OBJECTIVE: In rheumatoid arthritis (RA) joint erosion is accompanied by T cell infiltration of the synovial tissue. The resulting T cell receptor (TCR) repertoire is a combination of antigen driven shaping, nonspecific selection by endothelial cell-T cell interactions, and cytokine mediated chemoattraction. Considering the conflicting results of molecular biology studies of the TCR repertoire in RA, we attempted to obtain new data to clarify the situation through microscopic distribution analysis of TCR beta chain diversity in synovium follicular CD4/CD8 subsets. METHODS: We used dual color fluorescence confocal microscopy with CD4/CD8 monoclonal antibodies (Mab) and a panel of new anti-V beta Mab. The analysis focussed on lymphocyte rich, follicle-like areas of synovial tissue from 4 patients with RA. RESULTS: The expression of individual TCR beta families varied between areas within the T cell follicles, and between patients. Normal absolute levels of some beta chains can be completely skewed towards one subset, indicating that overall TCR evaluation is insufficient. CONCLUSION: Confocal microscopy analysis of localized TCR diversity in RA synovium offers novel insight into overall V beta gene usage, which appears to be the accumulation of several localized microexpansions.
Assuntos
Artrite Reumatoide/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Membrana Sinovial/metabolismo , Anticorpos Monoclonais , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Relação CD4-CD8 , Humanos , Microscopia Confocal , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Subpopulações de Linfócitos T/imunologia , Distribuição TecidualRESUMO
OBJECTIVE: We sought new susceptibility markers for rheumatoid arthritis (RA) among the T cell receptor gamma (TCR gamma) genes. METHODS: We analyzed restriction fragment length polymorphisms (RFLP) of the first variable subgroup of TCR gamma genes in a group of French control subjects and a group of French RA patients. RESULTS: No significant difference in Eco RI RFLP was found between the 2 study populations: Allele frequencies were virtually identical. There was no polymorphism using Hind III. CONCLUSION: These results exclude TCRV gamma I polymorphism as a disease susceptibility marker in RA.
Assuntos
Artrite Reumatoide/genética , Receptores de Antígenos de Linfócitos T gama-delta/genética , Artrite Reumatoide/imunologia , Southern Blotting , Haplótipos/genética , Humanos , Polimorfismo de Fragmento de Restrição , Valores de ReferênciaRESUMO
Using immunohistology and monoclonal antibodies directed to the T-cell receptor (TCR) chains, we have analysed the distribution of TCR-bearing lymphocytes within the membrane of rheumatoid arthritis (RA) patients. Alkaline phosphatase staining for TCR alpha beta-bearing lymphocytes showed a distribution paralleling that of the total T cells. Staining for the TCR gamma delta chains revealed a moderate and rather homogeneous distribution of T gamma delta lymphocytes within the RA synovium. As evidenced by simultaneous staining for alpha beta and gamma delta receptors, the relative count of T gamma delta to alpha beta-expressing cells is close to the peripheral count (e.g.5%), and lower than that previously observed in the synovial fluid. Interestingly, the peripheral type V gamma 9-J gamma P rearrangement using the T gamma delta cell subset was relatively decreased in the synovial membrane, as compared to synovial fluid and peripheral blood, suggesting that the T gamma delta distribution in the rheumatoid synovium resembles a thymic-like situation.