Homeostatic expansion occurs independently of costimulatory signals.
Naive T cells undergo homeostatic proliferation in lymphopenic mice, a process that involves TCR recognition of specific self peptide/MHC complexes. Since costimulation signals regulate the T cell response to foreign Ags, we asked whether they also regulate homeostatic expansion. We report in this study that homeostatic expansion of CD4 and CD8 T cells occurs independently of costimulation signals mediated through CD28/B7, CD40L/CD40, or 4-1BB/4-1BBL interactions. Using DO11.10 TCR transgenic T cells, we confirmed that CD28 expression was dispensable for homeostatic expansion, and showed that the presence of endogenous CD4(+)CD25(+) regulatory cells did not detectably influence homeostatic expansion. The implications of these findings with respect to regulation of T cell homeostasis and autoimmunity are discussed.
Prlic
M
M
Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
Blazar
B R
BR
Khoruts
A
A
Zell
T
T
Jameson
S C
SC
D053330:4-1BB Ligand; D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D019672:Genes, T-Cell Receptor; D006706:Homeostasis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D053330:4-1BB Ligand; D018106:CD28 Antigens; D019013:CD40 Antigens; D015375:Receptors, Interleukin-2; C505975:Tnfsf9 protein, mouse; D014409:Tumor Necrosis Factor-alpha