Cytokine synergy in antigen-independent activation and priming of naive CD8+ T lymphocytes.
Activation of naive T cells by antigen requires signaling via the T-cell receptor (TCR) and co-stimulatory receptors. However, in response to homeostatic pressure, T lymphocytes undergo cytokine-driven proliferation without overt antigen stimulation. Homeostatic expansion is more pronounced in the CD8+ T-cell compartment, with memory CD8+ T cells showing intense proliferation resulting from increased responsiveness to IL-15. On the other hand, naive CD8+ T cells require IL-7 and MHC-I to undergo homeostatic expansion, implying the requirement for a basal level of TCR signaling. Probably because of this strict requirement for MHC, earlier reports on antigen-independent stimulation of naive human CD8+ T cells by inflammatory cytokines did not receive much attention. Recently, we and others have shown that naive murine CD8+ T cells undergo proliferation following synergistic simulation by inflammatory cytokines. Such cytokine-driven, antigen-independent activation also "sensitizes" or "primes" naive CD8+ T cells, enabling them to respond robustly to limiting concentrations of cognate antigens, produce effector cytokines abundantly, and display potent cytolytic activity. We propose that cytokine synergy, which induces antigen-independent activation and priming of naive CD8+ T cells, may significantly contribute to the transition from innate to adaptive immune response and to inadvertent activation of autoreactive CD8+ T cells.
Ramanathan
Sheela
S
Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Sherbrooke; Centre de Recherche Clinique Etienne-Le Bel, Centre Hospitalier de I'Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
Gagnon
Julien
J
Dubois
Stephanie
S
Forand-Boulerice
Melissa
M
Richter
Martin V
MV
Ilangumaran
Subburaj
S
D000818:Animals; D000941:Antigens / Q000276:immunology; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D015851:Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D000941:Antigens; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell