IL-7R alpha(low) memory CD8(+) T cells are significantly elevated in patients with systemic lupus erythematosus

Abstract

Objective. Human effector memory (EM) CD8(+) T cells include IL-7R alpha(high) and IL-7R alpha(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-7R alpha(high) and IL-7R alpha(low) EM CD8(+) T cells and its contribution to cytotoxicity. We also analysed the frequency of IL-7R alpha(high) and IL-7R alpha(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-7R alpha(high) and IL-7R alpha(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-7R alpha(high) and IL-7R alpha(low) EM CD8(+) T cells using target cells with CD48 antigen. Results. We found that IL-7R alpha(high) EM CD8(+) T cells had higher levels of 2B4 expression compared with IL-7R alpha(low) EM CD8(+) T cells. Triggering 2B4 enhanced the cytotoxic function of IL-7R alpha(low) EM CD8(+) T cells against target cells. We also noticed that patients with SLE had an increased frequency of IL-7R alpha(low) EM CD8(+) T cells that correlated with disease manifestation. Conclusion. Our findings show that SLE patients have increased IL-7R alpha(low) EM CD8(+) T cells, possibly contributing to tissue damage through 2B4-mediated cytotoxicity.