Competition for self ligands restrains homeostatic proliferation of naive CD4 T cells

Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1185-90. doi: 10.1073/pnas.0334572100. Epub 2003 Jan 13.

Abstract

T cell antigen receptor (TCR) diversity is a critical feature of adaptive immunity. However, restriction of TCR diversity is a potential risk during immune reconstitution by homeostatic proliferation. What peripheral mechanisms are in place to maintain TCR diversity during recovery from lymphopenia? Here, we examine competition between several monoclonal CD4 T cell populations in RAG(-/-) and TCR Tg RAG(-/-) environments. The results suggest that specific self ligands constitute a critical limiting resource essential for homeostatic proliferation of naive CD4 T cells. In addition, T cells ignore large numbers of competitors as long as their TCR specificity is different and other non-MHC resources are not limiting. Therefore, the numbers of self ligands expressed in the periphery set the limits on TCR diversity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Division
  • Crosses, Genetic
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Immunohistochemistry
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / metabolism
  • Ligands
  • Lymphopenia / immunology
  • Mice
  • Mice, Inbred BALB C
  • Time Factors

Substances

  • Interleukin-2
  • Ligands