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Death and Baxes: mechanisms of lymphotrophic cytokines

  1. Author:
    Khaled, A. R.
    Durum, S. K.

  2. Author Address

    NCI, Sect Cytokines & Immun, Mol Immunoregulat Lab, Ctr Canc Res, Bldg 560,Room 31-71, Frederick, MD 21702 USA NCI, Sect Cytokines & Immun, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA Univ Cent Florida, Dept Mol Biol & Microbiol, Biomol Sci Ctr, Orlando, FL 32816 USA Durum SK NCI, Sect Cytokines & Immun, Mol Immunoregulat Lab, Ctr Canc Res, Bldg 560,Room 31-71, Frederick, MD 21702 USA
    1. Year: 2003
  2. Journal: Immunological Reviews
    1. 193
    2. 1
    3. Pages: 48-57
  4. Type of Article: Review
  1. Abstract:

    In this review, we briefly cover the critical requirements for interleukin-7 (IL-7) in thymocyte development and peripheral T- cell homeostasis. Part of the IL-7 effect is antiapoptotic or 'trophic' and we have studied the intracellular pathways involved in lymphocyte survival and death regulated by this cytokine. We review the evidence for a role of the JAK signal transducers and activators of transcription protein (STAT) pathway and phosphoinositide 3-kinase (PI3K)-AKT pathways in survival. The death pathway following IL-7 withdrawal is discussed in terms of the balance of BCL-2 vs. BAX and other death proteins and the role of metabolic disturbances involving glucose metabolism and intracellular pH. The IL-7 survival and death pathways in lymphocytes may be representative of many trophic factors in different cell types; yet we conclude that much of the mechanism remains to be discovered.

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