Antigen non-specific activation of CD8+ T lymphocytes by cytokines: relevance to immunity, autoimmunity and cancer
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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 na?ve CD8+ T cells require both cytokines and TCR signaling. Recent reports show certain combinations of cytokines can induce proliferation and effector functions of na?ve CD8+ T cells without concomitant stimulation via the TCR. While such antigen non-specific stimulation of na?ve 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 na?ve CD8+ T cells may lead to novel strategies of intervention for autoimmune diseases. On the other hand, in vitro expansion of na?ve CD8+ T cells by certain combinations of cytokines could be used to generate tumor-specific cells with ideal properties for cellular immunotherapy of cancer.
Publication order reference
Subburaj Ilangumaran, Ph.D., Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, 3001 North, 12th Avenue, Sherbrooke, J1H 5N4, Quebec, Canada