Maintenance and homeostatic proliferation of regulatory CD4 T cells occur independent of the thymus and of secondary lymphoid organs (104.7)

Abstract

Abstract In vivo manipulations that influence regulatory Foxp3+CD4+ T cells (Treg) homeostasis represent a valuable therapeutic mean for balancing immunity and regulation. However, the signals and the anatomical sites of Treg homeostasis are not completely defined. Therefore, we investigated the role of the thymus, and of secondary lymphoid organs (SLO) on Treg homeostasis in steady state. The absolute numbers of conventional CD4 T cells (Tconv) and Treg in spleen, peripheral lymph nodes, bone marrow, blood, liver, and lungs were determined by flow cytometry in euthymic or thymectomized adult wt B6 mice and in mice lacking SLO (splenectomized Lymphotoxin receptor β knockout). Proliferation was measured by EdU incorporation over a period of 3 days prior to analysis. We found that, in wt B6 mice, Treg exhibited a much higher rate of homeostatic proliferation (HP) than Tconv in both lymphoid and non-lymphoid compartments. Thymectomy of adult B6 mice reduced Tconv numbers in all compartments by 30-60%, while Treg numbers remained primarily unaffected (d30 and d60). In absence of SLO or both thymus and SLO, Treg accumulated in non-lymphoid organs, in blood, and in bone marrow in higher numbers and displayed similar rates of HP compared to wt mice. Our data show that Treg homeostasis occurs independently of thymic production and of SLO, suggesting an intrinsic Treg ability to respond to antigens in non-lymphoid tissues.