CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor

Rebecca S McHugh; Matthew J Whitters; Ciriaco A Piccirillo; Deborah A Young; Ethan M Shevach; Mary Collins; Michael C Byrne

doi:10.1016/s1074-7613(02)00280-7

CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor

Immunity. 2002 Feb;16(2):311-23. doi: 10.1016/s1074-7613(02)00280-7.

Authors

Rebecca S McHugh¹, Matthew J Whitters, Ciriaco A Piccirillo, Deborah A Young, Ethan M Shevach, Mary Collins, Michael C Byrne

Affiliation

¹ Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

PMID: 11869690
DOI: 10.1016/s1074-7613(02)00280-7

Abstract

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.

MeSH terms

Animals
Antibodies, Monoclonal / metabolism
Antigens, CD / genetics
Biomarkers
CD4 Antigens*
CD4-Positive T-Lymphocytes / drug effects
CD4-Positive T-Lymphocytes / metabolism*
Cell Separation
Female
Gene Expression Profiling
Gene Expression*
Glucocorticoid-Induced TNFR-Related Protein
Glucocorticoids / pharmacology
Integrin alpha Chains*
Interleukin-2 / genetics
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Oligonucleotide Array Sequence Analysis
Receptors, Cell Surface / genetics
Receptors, Interleukin-2*
Receptors, Nerve Growth Factor / genetics
Receptors, Nerve Growth Factor / immunology
Receptors, Nerve Growth Factor / physiology*
Receptors, Tumor Necrosis Factor / genetics
Receptors, Tumor Necrosis Factor / immunology
Receptors, Tumor Necrosis Factor / physiology*

Substances

Antibodies, Monoclonal
Antigens, CD
Biomarkers
CD4 Antigens
Glucocorticoid-Induced TNFR-Related Protein
Glucocorticoids
Integrin alpha Chains
Interleukin-2
Receptors, Cell Surface
Receptors, Interleukin-2
Receptors, Nerve Growth Factor
Receptors, Tumor Necrosis Factor
Tnfrsf18 protein, mouse
alpha E integrins