IL-7 drives Th1 and Th17 cytokine production in patients with primary SS despite an increase in cd4 t cells lacking the IL-7Rα

Abstract

Objective: To study the phenotypic characteristics of and the balance between systemic IL-7 receptor (IL-7R)α + and IL-7Rα - Tregs in primary SS (pSS) patients as compared with control subjects and to assess the functional consequences this has for (IL-7-induced) T-cell activation.Methods. The functional properties of IL-7Rα + and IL-7Rα -(CD25 +) CD4 T cells from pSS patients were tested in vitro. Expression of CD25 and FoxP3 by IL-7Rα + and IL-7Rα -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-7Rα + 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-7Rα -CD25 + T cells expressing high levels of FoxP3, but also by increases in IL-7Rα -CD25 - CD4 T cells that only moderately expressed FoxP3. This altered balance in IL-7Rα + and IL-7Rα -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-7Rα -CD25 + T cells did not prevent specific IL-7-induced Th1 and Th17 cytokine production by IL-7Rα + T cells.Conclusion. IL-7Rα + cells are highly proliferating cells that respond strongly to IL-7 despite an increased number of IL-7Rα - T cells that express FoxP3 and CD25. The recent finding that IL-7 and IL-7Rα + 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-7Rα + responder T cells despite the increased numbers of Tregs. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.