IL-21 promotes survival and maintains a naive phenotype in human CD4+ T lymphocytes.
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.
Transplantation Immunology Unit, Division of Immunology and Allergy, Department of Internal Medicine, University Hospital and Faculty of Medicine, Geneva, Switzerland. sylvie.ferrari@hcuge.ch
Sylvie
S
Ferrari-Lacraz
Rachel
R
Chicheportiche
Gregory
G
Schneiter
Nicolas
N
Molnarfi
Jean
J
Villard
Jean-Michel
JM
Dayer
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology*; D054421:Chemokine CCL21 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D016130:Immunophenotyping; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D054400:Receptors, CCR7 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D000098546:Interleukin-21
C515370:CCR7 protein, human; D054421:Chemokine CCL21; D016207:Cytokines; D007378:Interleukins; D054400:Receptors, CCR7; D011994:Recombinant Proteins; D000098546:Interleukin-21