PLZF+ innate T cells support TGF-b-dependent generation of activated/memory-like regulatory T cells

Abstract

PLZF-expressing NKT cells and T-T CD4 T cells are unique subsets of innate T cells. Both of them are selected via thymocyte-thymocyte (T-T) interaction and simultaneously produce IL-4 and IFN-gama. Recently, it was reported that these PLZF+ cells contributed to the generation of effector/memory-like CD4 and CD8 T cells in the thymus. Based on these previous findings, we investigated the possible role of PLZF+ innate T cells in the development and function of CD4+ Foxp+ regulatory T cells in CIITATgPIV-/- mice. In contrast to the counterparts in wild type, Foxp3+ regulatory T cells in these mice exhibited effector/memory-like phenotype: up-regulation of surface molecules associated with regulatory functions (CD39 and CD73) and migrations (CCR4), and efficiently suppressed ovalbumin-induced allergic airway inflammation. During the course of intrathymic development, IL-4 produced by thymic PLZF+ T cells cooperated with TGF-beta for the acquisition of effector/memory phenotype of regulatory T cells. This is also the case in BALB/c mice where PLZF+ iNKT cells were the main source of IL-4. Thus, PLZF+ innate T cells modulate the thymic development of regulatory T cells as well as effector T cells.