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.

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