CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor.
CD4(+)CD25(+) immunoregulatory T cells represent a unique lineage of thymic-derived cells that potently suppress both in vitro and in vivo effector T cell function. We analyzed CD4(+)CD25(+) and CD4(+)CD25(-) T cells by DNA microarray, identifying 29 genes differentially expressed in the resting subpopulations, and 77 that were differentially expressed following activation. Most of these genes were elevated in the CD4(+)CD25(+) population, suggesting a previously activated phenotype. Among these were a number of genes that antagonize signaling, including members of the SOCS family, which may contribute to their anergic phenotype. Multiple cell surface receptors also had increased expression in CD4(+)CD25(+) cells, including GITR, a member of the TNF receptor superfamily. Importantly, antibodies to GITR abrogated suppression, demonstrating a functional role for this receptor in regulating the CD4(+)CD25(+) T cell subset.
McHugh
Rebecca S
RS
Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Whitters
Matthew J
MJ
Piccirillo
Ciriaco A
CA
Young
Deborah A
DA
Shevach
Ethan M
EM
Collins
Mary
M
Byrne
Michael C
MC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics; D015415:Biomarkers; D015704:CD4 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002469:Cell Separation; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D053450:Glucocorticoid-Induced TNFR-Related Protein; D005938:Glucocorticoids / Q000494:pharmacology; D039001:Integrin alpha Chains; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011956:Receptors, Cell Surface / Q000235:genetics; D015375:Receptors, Interleukin-2; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015415:Biomarkers; D015704:CD4 Antigens; D053450:Glucocorticoid-Induced TNFR-Related Protein; D005938:Glucocorticoids; D039001:Integrin alpha Chains; D007376:Interleukin-2; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C106544:Tnfrsf18 protein, mouse; C091367:alpha E integrins