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

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Published in International immunology. 2008, vol. 20, no. 8, p. 1009-18
Abstract 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 AdultCD4-Positive T-Lymphocytes/cytology/immunology/metabolismCell Movement/immunologyCell Proliferation/drug effectsCell Survival/drug effects/immunologyChemokine CCL21/agonists/immunology/metabolismCytokines/secretionHomeostasis/drug effects/immunologyHumansImmunologic Memory/drug effects/immunologyImmunophenotypingInterleukins/immunology/metabolism/pharmacologyLymphocyte Activation/drug effects/immunologyReceptors, CCR7/agonists/immunology/metabolismRecombinant Proteins/immunology/metabolism/pharmacologySignal Transduction/immunology
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PMID: 18556671
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Other version: http://intimm.oxfordjournals.org/cgi/content/full/20/8/1009
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Research groups Transplantation Immunologie et Osteoimmunologie (561)
Inflammation et allergie (874)
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FERRARI-LACRAZ, Sylvie et al. IL-21 promotes survival and maintains a naive phenotype in human CD4+ T lymphocytes. In: International immunology, 2008, vol. 20, n° 8, p. 1009-18. https://archive-ouverte.unige.ch/unige:2542

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Deposited on : 2009-08-28

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