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Antigen-nonspecific activation of CD8+ T lymphocytes by cytokines: relevance to immunity, autoimmunity, and cancer

  • Sheela Ramanathan
  • Julien Gagnon
  • Subburaj Ilangumaran
REVIEW

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.

Keywords:

CD8+ T lymphocytes cytokines immune response autoimmunity cancer 

Copyright information

© Birkhaueser 2008

Authors and Affiliations

  • Sheela Ramanathan
    • 1
  • Julien Gagnon
    • 1
  • Subburaj Ilangumaran
    • 1
  1. 1.Immunology Division, Department of Pediatrics, Faculty of Medicine and Health SciencesUniversity of Sherbrooke; Centre de recherche clinique Etienne-Le Bel, Centre Hospitalier de l’université de SherbrookeSherbrookeCanada

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