IL-21 Sustains CD28 Expression on IL-15-Activated Human Naive CD8+ T Cells
Copyright policy )IL-21 Sustains CD28 Expression on IL-15-Activated Human Naive CD8+ T Cells
Abstract 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 γ-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-γ 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.
- Universidade Lusófona do Porto Portugal
- Amsterdam University Medical Centers Netherlands
- Amsterdam UMC Netherlands
- INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR-IBMC Portugal
Interleukin-15, Interleukin-7, Interleukins, Dose-Response Relationship, Immunologic, Down-Regulation, Interleukin-21 Receptor alpha Subunit, Receptors, Interleukin, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Interferon-gamma, Protein Subunits, Adjuvants, Immunologic, CD28 Antigens, Humans, Interleukin-2, Receptors, Interleukin-21, RNA, Messenger, Cells, Cultured, Cell Proliferation, Interleukin Receptor Common gamma Subunit
Interleukin-15, Interleukin-7, Interleukins, Dose-Response Relationship, Immunologic, Down-Regulation, Interleukin-21 Receptor alpha Subunit, Receptors, Interleukin, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Interferon-gamma, Protein Subunits, Adjuvants, Immunologic, CD28 Antigens, Humans, Interleukin-2, Receptors, Interleukin-21, RNA, Messenger, Cells, Cultured, Cell Proliferation, Interleukin Receptor Common gamma Subunit
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