Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0806494 on June 6, 2007

Published online before print June 6, 2007
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(Journal of Leukocyte Biology. 2007;82:645-656.)
© 2007 by Society for Leukocyte Biology

IL-21 promotes T lymphocyte survival by activating the phosphatidylinositol-3 kinase signaling cascade

Valérie Ostiguy*,{dagger}, Ève-Line Allard*,{ddagger}, Miriam Marquis*,{ddagger}, Julie Leignadier*,{ddagger} and Nathalie Labrecque*,{dagger},1

* Maisonneuve-Rosemont Hospital Research Center, Departments of
{dagger} Medicine and
{ddagger} Microbiology and Immunology, University of Montreal, Montreal, Quebec, Canada

1 Correspondence: Research Center, Maisonneuve-Rosemont Hospital, 5415 boul. de l’Assomption, Montreal, Qc, Canada HIT 2M4. E-mail: nathalie.labrecque{at}umontreal.ca

IL-21 is a Type I cytokine, which uses the common {gamma} chain ({gamma}c) in its receptor. As members of the {gamma}c cytokine/cytokine receptors family play crucial role in the differentiation, activation, and survival of lymphocytes, we have investigated if IL-21 could promote T cell survival and thus, contribute to T cell homeostasis and expansion. Unlike most {gamma}c cytokine receptors, we report that IL-21R is constitutively expressed by all mature T lymphocytes and that stromal cells of lymphoid organs are a constitutive source of IL-21. These observations are reminiscent of what is observed for IL-7/IL-7R, which control T cell survival and homeostasis and suggest a role for IL-21 in T cell homeostasis. Indeed, our results show that IL-21 is a survival factor for resting and activated T cells. Moreover, the ability of IL-21 to costimulate T cell proliferation is mediated by enhancing T cell viability. Further investigation of how IL-21R signaling induces T cell survival shows for the first time that IL-21 binding to its receptor activates the PI-3K signaling pathway and induces Bcl-2 expression. Moreover, the activation of the PI-3K signaling pathway is essential for IL-21-mediated T cell survival. Our data provide a new role for IL-21 in the immune system, which might be used to improve T cell homeostasis in immunocompromised patients.

Key Words: cytokine • cytokine receptor • homeostasis • Bcl-2




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