Antigen-nonspecific activation of CD8+ T lymphocytes by cytokines: relevance to immunity, autoimmunity, and cancer.
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.
Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
Sheela
S
Ramanathan
Julien
J
Gagnon
Subburaj
S
Ilangumaran
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007109:Immunity; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction
D016207:Cytokines; D011948:Receptors, Antigen, T-Cell