Antigen-nonspecific activation of CD8+ T lymphocytes by cytokines: relevance to immunity, autoimmunity, and cancer |
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Authors: | Sheela Ramanathan Julien Gagnon Subburaj Ilangumaran PhD |
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Institution: | (1) Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Sherbrooke; Centre de recherche clinique Etienne-Le Bel, Centre Hospitalier de l’université de Sherbrooke, 3001 North, 12th Avenue, Sherbrooke, J1H 5N4, Québec, Canada |
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Abstract: | Development of T lymphocytes and their survival in the periphery are dependent on signals emanating from cytokine receptors as well as the T cell antigen receptor (TCR). These two signaling pathways play distinct and complementary roles at various stages of T cell development, maturation, survival, activation and differentiation. During immune response to foreign antigens initiated by TCR signaling, cytokines play a key role in the expansion of activated T cells. Even though the initial activation of T cells occurs via the TCR, this requirement can be overcome under certain circumstances. During lymphopenia, cytokines trigger memory CD8+ T cells to undergo antigen non-specific homeostatic expansion, whereas naïve CD8+ T cells require both cytokines and TCR signaling. Recent reports show certain combinations of cytokines can induce proliferation and effector functions of naïve CD8+ T cells without concomitant stimulation via the TCR. While such antigen non-specific stimulation of naïve T cells might significantly boost the adaptive immune response, it could also have an undesirable effect of triggering potentially autoreactive cells. Understanding the mechanisms and the regulation of cytokine-driven stimulation of naïve CD8+ T cells may lead to novel strategies of intervention for autoimmune diseases. On the other hand, in vitro expansion of naïve CD8+ T cells by certain combinations of cytokines could be used to generate tumor-specific cells with ideal properties for cellular immunotherapy of cancer. |
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Keywords: | :" target="_blank">: CD8+ T lymphocytes cytokines immune response autoimmunity cancer |
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