Cytokine Synergy in Antigen-Independent Activation and Priming of Naive CD8+ T Lymphocytes
| Autor: | Sheela Ramanathan, Subburaj Ilangumaran, Stephanie Dubois, Melissa Forand-Boulerice, Julien Gagnon, Martin V. Richter |
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| Rok vydání: | 2009 |
| Předmět: |
Polymers and Plastics
Receptors Antigen T-Cell Priming (immunology) Autoimmunity CD8-Positive T-Lymphocytes Biology Lymphocyte Activation Mice Interleukin 21 Antigen T-Lymphocyte Subsets Animals Homeostasis Humans Cytotoxic T cell IL-2 receptor Antigens Cell Proliferation General Environmental Science Inflammation Interleukin-7 T-cell receptor CD28 Acquired immune system Immunity Innate Immunology Signal Transduction |
| Zdroj: | Critical Reviews™ in Immunology. 29:219-239 |
| ISSN: | 2162-6472 |
| DOI: | 10.1615/critrevimmunol.v29.i3.30 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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