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Due to its critical role in NK cell differentiation and CD8 +  T cell homeostasis, the importance of IL-15 is more firmly established for cytolytic effectors of the immune system than for CD4 +  T cells. The increased levels of IL-15 found in several CD4 +  T cell-driven (auto-) immune diseases prompted us to examine how IL-15 influences murine CD4 +  T cell responses to low dose TCR-stimulation  in vitro . We show that IL-15 exerts growth factor activity on both CD4 +  and CD8 +  T cells in a TCR-dependent and Cyclosporin A-sensitive manner. In CD4 +  T cells, IL-15 augmented initial IL-2-dependent expansion and once IL-15Rα was upregulated, IL-15 sustained the TCR-induced expression of IL-2/15Rβ, supporting proliferation independently of secreted IL-2. Moreover, IL-15 counteracts CD4 +  T cell suppression by a gradually expanding CD25 High CD4 +  T cell subset that expresses Foxp3 and originates from CD4 + CD25 +  Tregs. These  in vitro  data suggest that IL-15 may dramatically strengthen the T cell response to suboptimal TCR-triggering by overcoming an activation threshold set by Treg that might create a risk for autoimmune pathology.

IL-15 Augments TCR-Induced CD4+ T Cell Expansion In Vitro by Inhibiting the Suppressive Function of CD25High CD4+ T Cells