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Interleukin-7 (IL-7) plays a central role in the homeostasis of the T-cell compartment by regulating T-cell survival and proliferation. Whether IL-7 can influence T-cell receptor (TCR) signaling in T cells remains controversial. Here, using IL-7-deficient hosts and TCR-transgenic T cells that conditionally express IL-7R, we examined antigen-specific T-cell responses in vitro and in vivo to viral infection and lymphopenia to determine whether IL-7 signaling influences TCR-triggered cell division events. In vitro, we could find no evidence that IL-7 signaling could costimulate T-cell activation over a broad range of conditions, suggesting that IL-7 does not directly tune TCR signaling. In vivo, however, we found an acute requirement for IL-7 signaling for efficiently triggering T-cell responses to influenza A virus challenge. Furthermore, we found that IL-7 was required for the enhanced homeostatic TCR signaling that drives lymphopenia-induced proliferation by a mechanism involving efficient contacts of T cells with dendritic cells. 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 IL-7 in regulating T cell-dendritic cell interactions that is essential for both T-cell homeostasis and activation in vivo.

Original publication

DOI

10.1182/blood-2008-12-192252

Type

Journal article

Journal

Blood

Publication Date

04/06/2009

Volume

113

Pages

5793 - 5800

Keywords

Animals, Antigens, Dendritic Cells, Homeostasis, Interleukin-7, Lymphocyte Activation, Mice, Mice, Knockout, Receptors, Antigen, T-Cell, Receptors, Interleukin-7, Signal Transduction, Substrate Specificity, T-Lymphocytes