Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo.
CD4(+)CD25(+) suppressor T (TS) cells play a critical role in the maintenance of peripheral tolerance. We examined here proliferative and functional responses as well as differential gene expression in T(S) cells. We found that T(S) cells were hyporesponsive to antigenic stimuli in vivo and unable to flux Ca(2+) upon T cell receptor (TCR) engagement. However, T(S) cells were not impaired in their proliferative response to lymphopenia, which was dependent on major histocompatibility complex class II expression. Homeostatic proliferation did not abolish T(S) cell anergy; rather, it substantially augmented T(S) cell function. DNA array analyses identified genes that may inhibit responsiveness at a number of levels in multiple signaling cascades in T(S) cells, as well as several anti-apoptotic genes that may mediate their survival.
Gavin
Marc A
MA
Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, WA 98195, USA. mgavin@u.washington.edu
Clarke
Sally R
SR
Negrou
Ella
E
Gallegos
Alena
A
Rudensky
Alexander
A
D000818:Animals; D020296:Animals, Congenic; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D020013:Calcium Signaling; D002455:Cell Division; D002478:Cells, Cultured; D002633:Chemotaxis; D017635:Clonal Anergy / Q000276:immunology*; D020869:Gene Expression Profiling; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; C064658:RAG-1 protein