Increased antigen responsiveness of naive CD8 T cells exposed to IL-7 and IL-21 is associated with decreased CD5 expression.
Exposure of naive CD8 T cells to the synergistic combination of interleukin (IL)-7 and IL-21 enables them to respond strongly to subsequent antigen stimulation. Mechanisms underlying the increased antigen responsiveness of such cytokine-primed CD8 T cells remain unknown. In this study, we showed that a brief exposure of <24 h to IL-7 and IL-21 is sufficient enough to sensitize naive P14 T-cell receptor (TCR) transgenic CD8 T cells to respond to limiting quantities of antigen, resulting in increased proliferation, interferon-gamma secretion and antigen-specific cytolytic activity. Cytokine-induced increase in TCR responsiveness occurs even in the absence of costimulatory signals. Cytokine priming upregulates the expression of the gamma(c) chain and increases IL-2 production after antigen stimulation, thus enhancing autocrine stimulation. Notably, cytokine priming induces a rapid and profound downmodulation of CD5, implicated in the negative regulation of TCR signaling, by induction of the transcriptional repressor E47. These findings show that increased antigen responsiveness of cytokine-primed CD8 T cells results from the modulation of multiple cell-surface molecules, which influence cytokine receptor and TCR signaling.
Gagnon
Julien
J
Faculty of Medicine and Health Sciences, Immunology Division, Department of Pediatrics, University of Sherbrooke, Centre de Recherche Clinique Etienne-Le Bel, Centre Hospitalier de l'université de Sherbrooke, Québec, Canada.
Chen
Xi L
XL
Forand-Boulerice
Melissa
M
Leblanc
Chantal
C
Raman
Chander
C
Ramanathan
Sheela
S
Ilangumaran
Subburaj
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D018956:CD5 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D049109:Cell Proliferation; D015536:Down-Regulation / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015851:Interleukin-7 / Q000378:metabolism / Q000494:pharmacology*; D007378:Interleukins / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000098546:Interleukin-21
D000276:Adjuvants, Immunologic; D018956:CD5 Antigens; D015851:Interleukin-7; D007378:Interleukins; D000098546:Interleukin-21