Self-Recognition and the Regulation of Cd4+ T Cell Survival

  • Ronald N. Germain
  • Irena Stefanova
  • Jeffrey Dorfman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 512)


CD4+ T cells differentiate in the thymus from committed precursors to mature naive cells ready for peripheral circulation. Successful maturation depends on adequate but not excessive signaling upon T cell receptor (TCR) engagement of selfpeptide/MHC class II molecule ligands present in the thymic environment. Persistent TCR signaling throughout development from the CD4+CD8+ to the CD4+ state is required for completion of the developmental process. Recent work has suggested that a continuation of this signaling is essential for sustained survival of CD4+ T cells once they leave the thymus but our studies suggest otherwise. Although we found clear evidence for active TCR signaling involving recognition of self-ligands in peripheral lymphoid tissues, we did not see a substantial effect of loss of such signaling on the life-time of naive CD4+ T cells. Based on a careful review of the literature, we conclude that essentially all previous claims that MHC class II recognition plays a significant role in the survival of CD4+ T cells can be reinterpreted as an effect of self-recognition on proliferation in lymphopenic environments, maintaining population numbers without a marked effect on individual cell viability. We propose a possible explanation for why, in contrast, the viability of naive CD8+ T cells appears to show such self-MHC dependence and suggest that a primary function of self-recognition by T cells may be to enhance responses to foreign antigen.


Homeostatic Proliferation Naive Cell Lymphopenic Host Lymphopenic Environment Individual Cell Viability 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Ronald N. Germain
  • Irena Stefanova
  • Jeffrey Dorfman
    • 1
  1. 1.Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaUSA

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