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International Immunology Advance Access originally published online on June 12, 2008
International Immunology 2008 20(8):1009-1018; doi:10.1093/intimm/dxn059
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

IL-21 promotes survival and maintains a naive phenotype in human CD4+ T lymphocytes

Sylvie Ferrari-Lacraz1, Rachel Chicheportiche2, Gregory Schneiter1, Nicolas Molnarfi2, Jean Villard1 and Jean-Michel Dayer2

1 Transplantation Immunology Unit
2 Clinical Immunology Unit, Division of Immunology and Allergy, Department of Internal Medicine, University Hospital and Faculty of Medicine, Geneva, Switzerland

Correspondence to: S. Ferrari-Lacraz; E-mail: sylvie.ferrari{at}hcuge.ch

IL-21 is a key T-cell growth factor (TCGF) involved in innate and adaptive immune response. It contributes to the proliferation of naive, but not memory T lymphocytes. However, the full spectrum of IL-21 activity on T cells remains unclear. Here, we demonstrate that IL-21 primarily maintains the expression of specific naive cell surface markers such as CD45RA, CD27, CD62L and CCR7 on human CD4+ T lymphocytes and that the expression of CCR7 induces cell migration by means of CCL21 chemoattraction. These effects contrast with those of IL-2 which induced the marked proliferation of CD4+ T lymphocytes, leading to an activated-memory phenotype. Nevertheless, IL-21 maintained cell cycle activation and expression of proliferation markers, including proliferating cell nuclear antigen and Ki-67, and triggered T-cell proliferation via TCR and co-stimulation pathways. Unlike IL-2, IL-21 decreased the expression of the anti-apoptotic Bcl-2 protein, which correlated with the absence of activation of the phosphatidylinositol 3'-kinase/Akt signaling pathway. Thus, IL-21 is a TCGF whose function is the preservation of a pool of CD4+ T lymphocytes in a naive phenotype, with a low proliferation rate but with the persistence of cell cycling proteins and cell surface expression of CCR7. These findings strongly suggest that IL-21 plays a part in innate and adaptive immune response owing to homeostasis of T cells and their homing to secondary lymphoid organs.

Keywords: autoimmunity, CCR7, cytokines, T lymphocytes

Transmitting editor: H. Robson MacDonald

Received 18 October 2007, accepted 16 May 2008.


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