IL-21 sustains CD28 expression on IL-15-activated human naive CD8+ T cells.
Human naive CD8+ T cells are able to respond in an Ag-independent manner to IL-7 and IL-15. Whereas IL-7 largely maintains CD8+ T cells in a naive phenotype, IL-15 drives these cells to an effector phenotype characterized, among other features, by down-regulation of the costimulatory molecule CD28. We evaluated the influence of the CD4+ Th cell-derived common gamma-chain cytokine IL-21 on cytokine-induced naive CD8+ T cell activation. Stimulation with IL-21 did not induce division and only slightly increased IL-15-induced proliferation of naive CD8+ T cells. Strikingly, however, IL-15-induced down-modulation of CD28 was completely prevented by IL-21 at the protein and transcriptional level. Subsequent stimulation via combined TCR/CD3 and CD28 triggering led to a markedly higher production of IL-2 and IFN-gamma in IL-15/IL-21-stimulated cells compared with IL-15-stimulated T cells. Our data show that IL-21 modulates the phenotype of naive CD8+ T cells that have undergone IL-15 induced homeostatic proliferation and preserves their responsiveness to CD28 ligands.
Department of Experimental Immunology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. N.M.Lages.Alves@amu.uva.nl
Nuno L
NL
Alves
Fernando A
FA
Arosa
René A W
RA
van Lier
D000276:Adjuvants, Immunologic / Q000502:physiology; D018106:CD28 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15 / Q000037:antagonists & inhibitors / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis; D053738:Interleukin-21 Receptor alpha Subunit; D015851:Interleukin-7 / Q000502:physiology; D007378:Interleukins / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D021122:Protein Subunits / Q000096:biosynthesis; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053655:Receptors, Interleukin-21; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis; D016192:Resting Phase, Cell Cycle / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000098546:Interleukin-21
D000276:Adjuvants, Immunologic; D018106:CD28 Antigens; C508117:IL21R protein, human; C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15; D007376:Interleukin-2; D053738:Interleukin-21 Receptor alpha Subunit; D015851:Interleukin-7; D007378:Interleukins; D021122:Protein Subunits; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053655:Receptors, Interleukin-21; D020395:Receptors, Interleukin-7; D007371:Interferon-gamma; D000098546:Interleukin-21