RasGRP1‐dependent Signals Are Required For Regulatory T cell Survival and Function.

Abstract

Regulatory cells have been shown to have a critical role in controlling immune responses and preventing autoimmunity. In the absence of RasGRP1, mice develop a spontaneous lupus‐like disease, the reasons for which are poorly defined. T cell development is dramatically impaired by the loss of RasGRP1 and the diminished T cell population may be one factor for disease development. Given the important role of regulatory T cells, we undertook studies to monitor regulatory cell development and function in the absence of RasGRP1. Regulatory T cells develop normally in the absence of RasGRP1 and make up a larger portion of the CD4+ T cell pool than in wild type mice. Surprisingly, regulatory T cells from RasGRP1 mutant mice exhibit impaired function with increased susceptibility to apoptosis in vitro. We are currently testing in vivo regulatory cell function and investigating the reasons for the increased susceptibility to apoptosis. Together these data suggest that RasGRP1 is an important mediator of signals leading to both regulatory cell survival and function.