Self-class I MHC molecules support survival of naive CD8 T cells, but depress their functional sensitivity through regulation of CD8 expression levels

J Exp Med. 2009 Sep 28;206(10):2253-69. doi: 10.1084/jem.20082553. Epub 2009 Sep 14.


Previous studies have suggested that naive CD8 T cells require self-peptide-major histocompatability complex (MHC) complexes for maintenance. However, interpretation of such studies is complicated because of the involvement of lymphopenic animals, as lymphopenia drastically alters naive T cell homeostasis and function. In this study, we explored naive CD8 T cell survival and function in nonlymphopenic conditions by using bone marrow chimeric donors and hosts in which class I MHC expression is absent or limited to radiosensitive versus radioresistant cells. We found that long-term survival of naive CD8 T cells (but not CD4 T cells) was impaired in the absence of class I MHC. However, distinct from this effect, class I MHC deprivation also enhanced naive CD8 T cell responsiveness to low-affinity (but not high-affinity) peptide-MHC ligands. We found that this improved sensitivity was a consequence of up-regulated CD8 levels, which was mediated through a transcriptional mechanism. Hence, our data suggest that, in a nonlymphopenic setting, self-class I MHC molecules support CD8 T cell survival, but that these interactions also attenuate naive T cell sensitivity by dynamic tuning of CD8 levels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8 Antigens / genetics*
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Survival
  • Gene Expression Regulation
  • Histocompatibility Antigens Class I / physiology*
  • Immunophenotyping
  • Interleukin-7 Receptor alpha Subunit / analysis
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Interleukin-7 / physiology
  • Transplantation Chimera


  • CD8 Antigens
  • Histocompatibility Antigens Class I
  • Interleukin-7 Receptor alpha Subunit
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain