Distinct molecular program imposed on CD4+ T cell targets by CD4+CD25+ regulatory T cells.
CD4+CD25+ regulatory T cells (Tregs) are key modulators of immunity, but their mechanism of action is unclear. To elucidate the molecular consequences of Treg encounter, we analyzed changes in gene expression in CD4+ T cell targets activated in the presence or absence of CD4+CD25+ Tregs. Tregs did not alter the early activation program of CD4+ T cells, but had reversed many of the activation-induced changes by 36 h. It is not known whether Tregs simply induce a set of transcriptional changes common to other nonproliferative states or whether instead Tregs mediate a distinct biological activity. Therefore, we compared the gene profile of T cells following Treg encounter with that of T cells made anergic, TGF-beta-treated, or IL-2-deprived; all possible modes of Treg action. Strikingly, all genes down-regulated in suppressed cells were indeed common to these nonproliferative states. In contrast, Treg encounter led to elevated expression of a unique set of genes in the target T cells. Although different from the nonproliferative states tested, the Treg-imposed gene program is exemplified by expression of many genes associated with growth arrest or inhibition of proliferation. We suggest that Tregs function by the induction of a distinct set of negative regulatory factors that initiate or maintain target T cells in a nonproliferative state.
Sukiennicki
Teresa L
TL
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester, Rochester, NY 14642, USA.
Fowell
Deborah J
DJ
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit