Interleukin-15 (IL-15) is essential for the survival of memory CD8+ and CD4+ T cell subsets, and natural killer and natural killer T cells. Here, we describe a hitherto unreported role of IL-15 in regulating homoeostasis of naive CD4+ T cells. Adoptive transfer of splenocytes from non-obese diabetic (NOD) mice results in increased homeostatic expansion of T cells in lymphopenic NOD.scid.Il15-/- mice when compared to NOD.scid recipients. The increased accumulation of CD4+ T cells is also observed in NOD.Il15-/- mice, indicating that IL-15-dependent regulation also occurs in the absence of lymphopenia. NOD.scid mice lacking the IL-15Rα chain, but not those lacking the common gamma chain, also show increased... More
Interleukin-15 (IL-15) is essential for the survival of memory CD8+ and CD4+ T cell subsets, and natural killer and natural killer T cells. Here, we describe a hitherto unreported role of IL-15 in regulating homoeostasis of naive CD4+ T cells. Adoptive transfer of splenocytes from non-obese diabetic (NOD) mice results in increased homeostatic expansion of T cells in lymphopenic NOD.scid.Il15-/- mice when compared to NOD.scid recipients. The increased accumulation of CD4+ T cells is also observed in NOD.Il15-/- mice, indicating that IL-15-dependent regulation also occurs in the absence of lymphopenia. NOD.scid mice lacking the IL-15Rα chain, but not those lacking the common gamma chain, also show increased accumulation of CD4+ T cells. These findings indicate that the IL-15-mediated regulation occurs directly on CD4+ T cells and requires trans-presentation of IL-15. CD4+ T cells expanding in the absence of IL-15 signaling do not acquire the characteristics of classical regulatory T cells. Rather, CD4+ T cells expanding in the absence of IL-15 show impaired antigen-induced activation and IFN-γ production. Based on these findings, we propose that the IL-15-dependent regulation of the naive CD4+ T-cell compartment may represent an additional layer of control to thwart potentially autoreactive cells that escape central tolerance, while permitting the expansion of memory T cells.Cellular & Molecular Immunology advance online publication, 24 March 2014; doi:10.1038/cmi.2014.13.
