Death and Baxes: mechanisms of lymphotrophic cytokines

Immunol Rev. 2003 Jun:193:48-57. doi: 10.1034/j.1600-065x.2003.00050.x.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Humans
  • Interleukin-3 / immunology
  • Interleukin-7 / immunology*
  • Proto-Oncogene Proteins / immunology*
  • Proto-Oncogene Proteins c-bcl-2*
  • Receptors, Interleukin-7 / immunology
  • Signal Transduction / immunology*
  • T-Lymphocytes / physiology*
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • Interleukin-3
  • Interleukin-7
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Interleukin-7
  • bcl-2-Associated X Protein