T ‐bet regulates differentiation of forkhead box protein 3 + regulatory T cells in programmed cell death‐1‐deficient mice

Summary Programmed cell death‐1 ( PD ‐1) plays an important role in peripheral T cell tolerance, but whether or not it affects the differentiation of helper T cell subsets remains elusive. Here we describe the importance of PD ‐1 in the control of T helper type 1 ( T h1) cell activation and development of forkhead box protein 3 (FoxP3 + ) regulatory T cells ( T regs ). PD ‐1‐deficient T cell‐specific T ‐bet transgenic ( P / T ) mice showed growth retardation, and the majority died within 10 weeks. P / T mice showed T ‐bet over‐expression, increased interferon ( IFN) ‐γ production by CD 4 + T cells and significantly low FoxP3 + T reg cell percentage. P / T mice developed systemic inflammation, which was probably induced by augmented T h1 response and low FoxP3 + T reg count. The study identified a unique, previously undescribed role for PD ‐1 in T h1 and T reg differentiation, with potential implication in the development of T h1 cell‐targeted therapy.