RELT negatively regulates the early phase of the T‐cell response in mice

摘要

Abstract RELT (tumor necrosis factor receptor superfamily member 19‐like, TNFRSF19L) is a TNFR superfamily member that is primarily expressed in immune cells and lymphoid tissues, but whose immunological function is not well‐defined. Here, we show that RELT is expressed by naive T?cells and DCs, and their activation or maturation decreases RELT expression. Using RELT knockout (RELT ?/? ) mice, we demonstrate that RELT deficiency selectively promotes the homeostatic proliferation of CD4 + T?cells but not CD8 + T?cells, and enhances anti‐tumor CD8 + T‐cell responses. We also demonstrate, using an adoptive transfer model in which RELT is knocked‐out in either the transferred transgenic CD8 + T?cells or the recipient melanoma‐bearing mice, that RELT on multiple immune cells limits the hyper‐response of tumor‐specific CD8 + T?cells. Hyper‐responsiveness of RELT‐deficient T?cells was induced by promoting their proliferation. Taken together, our findings suggest that RELT acts as a negative regulator that controls the early phase of T‐cell activation probably by promoting T‐cell apoptosis.