CD28 regulates glucocorticoid-induced TNF receptor family-related gene expression on CD4+ T cells via IL-2-dependent mechanisms

Cell Immunol. 2005 May;235(1):56-64. doi: 10.1016/j.cellimm.2005.07.002. Epub 2005 Aug 30.

Abstract

The glucocorticoid-induced TNF-related gene receptor (GITR) is the newest member of the costimulatory molecule family and is expressed on both resting CD4+CD25+ regulatory T (T(R)) cells and activated CD4+ T cells. We investigated the endogenous mechanisms that regulate GITR expression on both T(R) and CD4+ T cells, as well as the functional interaction between GITR and other costimulatory molecules. CD28 stimulation increased GITR expression on both T(R) and CD4+ T cells via IL-2-dependent mechanisms. In addition, ligation of GITR and/or CD28 increased the level of CD4+ T cell proliferation and effector function under both APC-dependent and -independent conditions, suggesting that these costimulatory molecules cooperate to regulate CD4+ T cell activation and function by directly signaling to the CD4+ T cell. Thus, GITR may serve opposing functional roles on CD4+ T(R) and effector cells and alterations in GITR expression and/or function may tip the balance between immune tolerance and effector function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • CD28 Antigens / physiology*
  • Cells, Cultured
  • Gene Expression Regulation / immunology*
  • Glucocorticoid-Induced TNFR-Related Protein
  • Glucocorticoids / physiology*
  • Interleukin-2 / genetics
  • Interleukin-2 / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Multigene Family / immunology*
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-2 / deficiency
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism
  • Receptors, Nerve Growth Factor / biosynthesis*
  • Receptors, Nerve Growth Factor / genetics*
  • Receptors, Tumor Necrosis Factor / biosynthesis*
  • Receptors, Tumor Necrosis Factor / genetics*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / physiology*

Substances

  • Antibodies, Monoclonal
  • CD28 Antigens
  • Glucocorticoid-Induced TNFR-Related Protein
  • Glucocorticoids
  • Interleukin-2
  • RNA, Messenger
  • Receptors, Interleukin-2
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • Tnfrsf18 protein, mouse