Competition for self ligands restrains homeostatic proliferation of naive CD4 T cells.
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.
Moses
Christina T
CT
Department of Medicine, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
Thorstenson
Kristen M
KM
Jameson
Stephen C
SC
Khoruts
Alexander
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002455:Cell Division; D003433:Crosses, Genetic; D003713:Dendritic Cells / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D008024:Ligands; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors
D007376:Interleukin-2; D008024:Ligands