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Rheumatology (Oxford) ; 51(9): 1587-94, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22661557

RESUMO

OBJECTIVE: Human effector memory (EM) CD8(+) T cells include IL-7Rα(high) and IL-7Rα(low) cells with distinct cellular characteristics, including the expression of cytotoxic molecules. Both NK cells and the NK cell-associated molecule 2B4 that is expressed on CD8(+) T cells promote cytotoxicity. Here we analysed the expression of 2B4 on IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells and its contribution to cytotoxicity. We also analysed the frequency of IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells in patients with SLE or lupus and in healthy individuals given the potential role of cytotoxic CD8(+) T cells in the pathogenesis of lupus. METHODS: We used flow cytometry to measure the expression of 2B4 on IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells as well as the frequency of these cell populations in the peripheral blood of healthy individuals and patients with SLE. Also, 2B4-mediated cytotoxicity was quantitated in IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells using target cells with CD48 antigen. RESULTS: We found that IL-7Rα(high) EM CD8(+) T cells had higher levels of 2B4 expression compared with IL-7Rα(low) EM CD8(+) T cells. Triggering 2B4 enhanced the cytotoxic function of IL-7Rα(low) EM CD8(+) T cells against target cells. We also noticed that patients with SLE had an increased frequency of IL-7Rα(low) EM CD8(+) T cells that correlated with disease manifestation. CONCLUSION: Our findings show that SLE patients have increased IL-7Rα(low) EM CD8(+) T cells, possibly contributing to tissue damage through 2B4-mediated cytotoxicity.


Assuntos
Antígenos CD/metabolismo , Linfócitos T CD8-Positivos/imunologia , Memória Imunológica/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Receptores Imunológicos/metabolismo , Receptores de Interleucina-7/imunologia , Adulto , Anticorpos Bloqueadores/farmacologia , Antígenos CD/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Técnicas de Cocultura , Citotoxicidade Imunológica , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Lúpus Eritematoso Sistêmico/sangue , Contagem de Linfócitos , Receptores Imunológicos/imunologia , Receptores de Interleucina-7/metabolismo , Família de Moléculas de Sinalização da Ativação Linfocitária
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