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Critical Reviews™ in Immunology
インパクトファクター: 1.352 5年インパクトファクター: 3.347 SJR: 1.022 SNIP: 0.55 CiteScore™: 2.19

ISSN 印刷: 1040-8401
ISSN オンライン: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v29.i3.30
pages 219-239

Cytokine Synergy in Antigen-Independent Activation and Priming of Naive CD8+ T Lymphocytes

Sheela Ramanathan
Immunology Division, Department of Pediatrics, and Department of Medicine, University of Sherbrooke; Centre de Recherche Clinique Etienne-Le Bel, Centre Hospitalier de I'Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4
Julien Gagnon
Immunology Division, Department of Pediatrics, and Department of Medicine, University of Sherbrooke; Centre de Recherche Clinique Etienne-Le Bel, Centre Hospitalier de I'Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4
Stephanie Dubois
Immunology Division, Department of Pediatrics, and Department of Medicine, University of Sherbrooke; Centre de Recherche Clinique Etienne-Le Bel, Centre Hospitalier de I'Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4
Melissa Forand-Boulerice
Immunology Division, Department of Pediatrics, and Department of Medicine, University of Sherbrooke; Centre de Recherche Clinique Etienne-Le Bel, Centre Hospitalier de I'Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4
Martin V. Richter
Pulmonary Division, 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
Subburaj Ilangumaran
Immunology Division, Department of Pediatrics, and Department of Medicine, University of Sherbrooke; Centre de Recherche Clinique Etienne-Le Bel, Centre Hospitalier de I'Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4

要約

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.


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