Characterization of a new regulatory CD4 + T cell subset in primary Sjo¨gren’s syndrome RHEUMATOLOGY

Objective. CD4 + CD25 low GITR + T lymphocytes expressing FoxP3 and showing regulatory function have been recently described in healthy donors (HD). The objective of the study was to investigate their presence and role in patients with primary SS (pSS). Methods. CD4 + CD25 low GITR + cells circulating in peripheral blood (PB) of patients with pSS were isolated by MACS technique, their phenotype was studied by flow cytometry and real-time PCR, and their function was studied by in vitro co-culture. CD4 + CD25 low GITR + cells infiltrating salivary glands (SGs) were revealed by immunohistochemistry. Results. Results indicated that conventional CD4 + CD25 high regulatory T cells (Tregs) are decreased, whereas CD4 + CD25 low GITR + cells are expanded in the PB of pSS as compared with HD. Phenotypic analysis demonstrated that CD4 + CD25 low GITR + cells display Treg markers, including FoxP3, TGF- b and IL-10, and functional experiments demonstrated that they exert a strong inhibitory activity against autologous effector cells. CD4 + CD25 low GITR + cells were detectable in great number in the SG inflammatory infiltrate. Interestingly, PB CD4 + CD25 low GITR + cell expansion was evident only in patients with inactive disease, while conventional CD4 + CD25 high Treg number was not associated with disease activity. Conclusion. The present data demonstrate that circulating CD4 + cells expressing GITR, but with low levels of CD25 (CD4 + CD25 low GITR + ), are detectable in pSS patients. These cells, displaying Treg phenotype and function, are present in SG inflamed tissues and are expanded in the PB of subjects with inactive disease. Data suggest that the expansion of CD4 + CD25 low GITR + cells in pSS may represent a counter-regulatory attempt against autoimmune-driven inflammation and may provide a new target for future treatment strategies.

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