Cutting Edge: The Natural Ligand for Glucocorticoid-Induced TNF Receptor-Related Protein Abrogates Regulatory T Cell Suppression

Hong Bin Ji, Gongxian Liao, William Alvis Faubion, Ana C. Abadía-Molina, Cristina Cozzo, F. Stephen Laroux, Andrew Caton, Cox Terhorst

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

CD4+25+ regulatory T (Treg) cells maintain immunological self-tolerance through mechanisms that are only in part understood. Previous studies suggest that the glucocorticoid-induced TNFR-related protein (GITR), which is preferentially expressed on the surface of Treg cells, potentially provides a signal that abrogates Treg suppression. In this study, we show that a soluble form of mouse GITR ligand (sGITR-L) induces GITR-dependent NF-κB activation and blocks in vitro suppression mediated by both resting and preactivated polyclonal and Ag-specific Treg cells. Since sGITR-L along with rIL-2 induces proliferation of CD4+25 + cells, it appears that sGITR-L can break the anergic state of Treg cells. Because sGITR-L also up-regulates IL-2 secretion by activated CD4 +25- T cells, these two sGITR-L induced signals synergize to interfere with suppressor activity by CD4+25+ Treg cells.

Original languageEnglish (US)
Pages (from-to)5823-5827
Number of pages5
JournalJournal of Immunology
Volume172
Issue number10
StatePublished - May 15 2004
Externally publishedYes

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Tumor Necrosis Factor Receptors
Regulatory T-Lymphocytes
Glucocorticoids
Ligands
Glucocorticoid-Induced TNFR-Related Protein
Proteins
Self Tolerance
Interleukin-2
Up-Regulation
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Ji, H. B., Liao, G., Faubion, W. A., Abadía-Molina, A. C., Cozzo, C., Laroux, F. S., ... Terhorst, C. (2004). Cutting Edge: The Natural Ligand for Glucocorticoid-Induced TNF Receptor-Related Protein Abrogates Regulatory T Cell Suppression. Journal of Immunology, 172(10), 5823-5827.

Cutting Edge : The Natural Ligand for Glucocorticoid-Induced TNF Receptor-Related Protein Abrogates Regulatory T Cell Suppression. / Ji, Hong Bin; Liao, Gongxian; Faubion, William Alvis; Abadía-Molina, Ana C.; Cozzo, Cristina; Laroux, F. Stephen; Caton, Andrew; Terhorst, Cox.

In: Journal of Immunology, Vol. 172, No. 10, 15.05.2004, p. 5823-5827.

Research output: Contribution to journalArticle

Ji, HB, Liao, G, Faubion, WA, Abadía-Molina, AC, Cozzo, C, Laroux, FS, Caton, A & Terhorst, C 2004, 'Cutting Edge: The Natural Ligand for Glucocorticoid-Induced TNF Receptor-Related Protein Abrogates Regulatory T Cell Suppression', Journal of Immunology, vol. 172, no. 10, pp. 5823-5827.
Ji, Hong Bin ; Liao, Gongxian ; Faubion, William Alvis ; Abadía-Molina, Ana C. ; Cozzo, Cristina ; Laroux, F. Stephen ; Caton, Andrew ; Terhorst, Cox. / Cutting Edge : The Natural Ligand for Glucocorticoid-Induced TNF Receptor-Related Protein Abrogates Regulatory T Cell Suppression. In: Journal of Immunology. 2004 ; Vol. 172, No. 10. pp. 5823-5827.
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