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Cloning and characterization of GITR ligand

Abstract

The gene encoding the natural ligand of murine glucocorticoid-induced tumor necrosis factor receptor (GITR) was cloned and characterized. The putative GITR ligand (GITRL) is composed of 173 amino acids with features resembling those of type II membrane proteins and is 51% identical to the human activation-inducible TNF receptor (AITR) ligand, TL6. Expression of the GITRL is restricted to immature and mature splenic dendritic cells. GITRL binds GITR expressed on HEK 293 cells and triggers NF-κB activation. Functional studies reveal that soluble CD8-GITRL prevents CD4+CD25+ regulatory T-cell-mediated suppressive activities.

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References

  1. Locksley RM, Killeen N, Lenardo MJ . The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 2001; 104: 487–501.

    Article  CAS  Google Scholar 

  2. Armitage RJ . Tumor necrosis factor receptor superfamily members and their ligands. Curr Opin Immunol 1994; 6: 407–413.

    Article  CAS  Google Scholar 

  3. Gruss HJ, Dower SK . Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas. Blood 1995; 85: 3378–3404.

    CAS  Google Scholar 

  4. Smith CA, Farrah T, Goodwin RG . The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 1994; 76: 959–962.

    Article  CAS  Google Scholar 

  5. Ronchetti S, Nocentini G, Riccardi C, Pandolfi PP . Role of GITR in activation response of T lymphocytes. Blood 2002; 100: 350–352.

    Article  CAS  Google Scholar 

  6. Nocentini G, Giunchi L, Ronchetti S et al. A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis. Proc Natl Acad Sci USA 1997; 94: 6216–6221.

    Article  CAS  Google Scholar 

  7. Nocentini G, Ronchetti S, Bartoli A et al. Identification of three novel mRNA splice variants of GITR. Cell Death Differ 2000; 7: 408–410.

    Article  CAS  Google Scholar 

  8. Kwon B, Yu KY, Ni J et al. Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand. J Biol Chem 1999; 274: 6056–6061.

    Article  CAS  Google Scholar 

  9. Shimizu J, Yamazaki S, Takahashi T, Sakaguchi YS . Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 2002; 3: 135–142.

    Article  CAS  Google Scholar 

  10. McHugh RS, Whitters MJ, Piccirillo CA et al. CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 2002; 16: 311–323.

    Article  CAS  Google Scholar 

  11. Gurney AL, Marsters SA, Huang RM et al. Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR. Curr Biol 1999; 9: 215–218.

    Article  CAS  Google Scholar 

  12. Mosialos G, Birkenbach M, Yalamanchili R, VanArsdale T, Ware C, Kieff E . The Epstein–Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell 1995; 80: 389–399.

    Article  CAS  Google Scholar 

  13. Rothe M, Sarma V, Dixit VM, Goeddel DV . TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40. Science 1995; 269: 1424–1427.

    Article  CAS  Google Scholar 

  14. Schindler U, Baichwal VR . Three NF-κB binding sites in the human E-selectin gene required for maximal tumor necrosis factor alpha-induced expression. Mol Cell Biol 1994; 14: 5820–5831.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Dr Shimon Sakaguchi for providing the DTA-1 hybridoma. This work was supported by the SRC Fund to the IRC at the University of Ulsan from KOSEF and the Ministry of Science and Technology, Korea, and US Public Health Service Grants R01EY013325 and P30EY02377 from the National Eye Institute, National Institutes of Health, Bethesda, MD, USA

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Correspondence to B S Kwon.

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Kim, J., Choi, B., Bae, J. et al. Cloning and characterization of GITR ligand. Genes Immun 4, 564–569 (2003). https://doi.org/10.1038/sj.gene.6364026

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