Published online before print June 6, 2007
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Article |
,
,,,@
*Maisonneuve-Rosemont Hospital Research Center, Departments of Medicine and Microbiology and Immunology, University of Montreal, Montreal, Quebec, Canada
@ To whom correspondence should be addressed. E-mail: nathalie.labrecque{at}umontreal.ca.
IL-21 is a Type I cytokine, which uses the common 
chain (c) in its receptor. As members of the 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 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
This article has been cited by other articles:
 |
|
 |
|
  A. Iannello, M.-R. Boulassel, S. Samarani, O. Debbeche, C. Tremblay, E. Toma, J.-P. Routy, and A. Ahmad Dynamics and Consequences of IL-21 Production in HIV-Infected Individuals: A Longitudinal and Cross-Sectional Study J. Immunol., January 1, 2010; 184(1): 114 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Leignadier, M.-P. Hardy, M. Cloutier, J. Rooney, and N. Labrecque Memory T-lymphocyte survival does not require T-cell receptor expression PNAS, December 23, 2008; 105(51): 20440 - 20445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ferrari-Lacraz, R. Chicheportiche, G. Schneiter, N. Molnarfi, J. Villard, and J.-M. Dayer IL-21 promotes survival and maintains a naive phenotype in human CD4+ T lymphocytes Int. Immunol., August 1, 2008; 20(8): 1009 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Caprioli, M. Sarra, R. Caruso, C. Stolfi, D. Fina, G. Sica, T. T. MacDonald, F. Pallone, and G. Monteleone Autocrine Regulation of IL-21 Production in Human T Lymphocytes J. Immunol., February 1, 2008; 180(3): 1800 - 1807. [Abstract] [Full Text] [PDF]
|
|
