IL-7 drives Th1 and Th17 cytokine production in patients with primary SS despite an increase in CD4 T cells lacking the IL-7Rα

Methods. The functional properties of IL-7R alpha(+) and IL-7R alpha(-)(CD25(+)) CD4 T cells from pSS patients were tested in vitro. Expression of CD25 and FoxP3 by IL-7R alpha(+) and IL-7R alpha(-)CD4 T cells from pSS patients and healthy controls (HCs) were assessed. Also, the net ex vivo T-cell cytokine production and the capacity of IL-7 to activate total CD4 T cells from pSS patients compared with HCs in vitro was tested. Results. IL-7R alpha(+) T cells from pSS patients strongly proliferated and their numbers were slightly reduced compared with HCs. This reduced number was caused by an increase in both anergic and suppressive IL-7R alpha(-)CD25(+) T cells expressing high levels of FoxP3, but also by increases in IL-7R alpha(-)CD25(-) CD4 T cells that only moderately expressed FoxP3. This altered balance in IL-7R alpha(+) and IL-7R alpha(-)CD4 T cells was accompanied by unchanged ex vivo Th1, Th2 and Th17 cytokine production of total CD4 T cells. Furthermore, the increased numbers of IL-7R alpha(-)CD25(+) T cells did not prevent specific IL-7-induced Th1 and Th17 cytokine production by IL-7R alpha(+) T cells. Conclusion. IL-7R alpha(+) cells are highly proliferating cells that respond strongly to IL-7 despite an increased number of IL-7R alpha(-) T cells that express FoxP3 and CD25. The recent finding that IL-7 and IL-7R alpha(+) T cells were both found to be increased in exocrine glands of pSS patients indicates that IL-7 could contribute to glandular inflammation by activation of IL-7R alpha(+) responder T cells despite the increased numbers of Tregs.