Submitted December 1, 2008
Accepted March 30, 2009
Regulation of T cell-dendritic cell interactions by IL7 governs T cell activation and homeostasis
Manoj Saini, Claire Pearson, and Benedict Seddon*
MRC Centre for Immune Regulation, Division of Immunity and Infection, Birmingham University, Birmingham, United Kingdom
Division of Immune Cell Biology, National Institute for Medical Research, London, United Kingdom
* Corresponding author; email: bseddon{at}nimr.mrc.ac.uk.
Interleukin-7 (IL7) plays a central role in the homeostasis of the T cell compartment by regulating T cell survival and proliferation. Whether IL7 can influence TCR signalling in T cells remains controversial. Here, using IL7 deficient hosts and TCR transgenic T cells that conditionally express IL7R, we examined antigen specific T cell responses in vitro and in vivo to viral infection and lymphopenia to ask whether IL7 signalling influences TCR triggered cell division events. In vitro, we could find no evidence that IL7 signalling could co-stimulate T cell activation over a broad range of conditions suggesting that IL7 does not directly tune TCR signalling. In vivo, however, we found an acute requirement for IL7 signalling for efficiently triggering T cell responses to influenza A virus challenge. Furthermore, we found that IL7 was required for the enhanced homeostatic TCR signalling that drives lymphopenia induce proliferation by a mechanism involving efficient contacts of T cells with dendritic cells (DCs). Consistent with this, saturating antigen presenting capacity in vivo overcame the triggering defect in response to cognate peptide. Thus, we demonstrate a novel role for IL7 in regulating T cell-DC interactions that is essential for both T cell homeostasis and activation in vivo.
