Cooperation of invariant NKT cells and CD4+CD25+ T regulatory cells in the prevention of autoimmune myasthenia

Ruolan Liu, Antonio La Cava, Xue Feng Bai, Youngheun Jee, Mary Price, Denise I. Campagnolo, Premkumar Christadoss, Timothy L. Vollmer, Luc Van Kaer, Fu Dong Shi

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Abstract

CD1d-restricted NKT cells and CD4+CD25+ regulatory T (Treg) cells are thymus-derived subsets of regulatory T cells that have an important role in the maintenance of self-tolerance. Whether NKT cells and Treg cells cooperate functionally in the regulation 1 of autoimmunity is not known. We have explored this possibility in experimental autoimmune myasthenia gravis (EAMG), an animal model of human myasthenia gravis, induced by immunization of C57BL/6 mice with the autoantigen acetylcholine receptor. We have demonstrated that activation of NKT cells by a synthetic glycolipid agonist of NKT cells, α-galactosylceramide (α-GalCer), inhibits the development of EAMG. α-GalCer administration in EAMG mice increased the size of the Treg cell compartment, and augmented the expression of foxp3 and the potency of CD4 +CD25+ cells to inhibit proliferation of autoreactive T cells. Furthermore, α-GalCer promoted NKT cells to transcribe the IL-2 gene and produce IL-2 protein. Depletion of CD25+ cells or neutralization of IL-2 reduced the therapeutic effect of α-GalCer in this model. Thus, α-GalCer-activated NKT cells can induce expansion of CD4 +CD25+ Treg cells, which in turn mediate the therapeutic effects of α-GalCer in EAMG. Induced cooperation of NKT cells and Treg cells may serve as a superior strategy to treat autoimmune disease.

Original languageEnglish (US)
Pages (from-to)7898-7904
Number of pages7
JournalJournal of Immunology
Volume175
Issue number12
StatePublished - Dec 15 2005

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Natural Killer T-Cells
Regulatory T-Lymphocytes
Autoimmune Experimental Myasthenia Gravis
Interleukin-2
Therapeutic Uses
Galactosylceramides
Self Tolerance
Myasthenia Gravis
Glycolipids
Autoantigens
Cholinergic Receptors
Autoimmunity
Inbred C57BL Mouse
Thymus Gland
Autoimmune Diseases
Immunization
Animal Models
T-Lymphocytes
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Liu, R., Cava, A. L., Bai, X. F., Jee, Y., Price, M., Campagnolo, D. I., ... Shi, F. D. (2005). Cooperation of invariant NKT cells and CD4+CD25+ T regulatory cells in the prevention of autoimmune myasthenia. Journal of Immunology, 175(12), 7898-7904.

Cooperation of invariant NKT cells and CD4+CD25+ T regulatory cells in the prevention of autoimmune myasthenia. / Liu, Ruolan; Cava, Antonio La; Bai, Xue Feng; Jee, Youngheun; Price, Mary; Campagnolo, Denise I.; Christadoss, Premkumar; Vollmer, Timothy L.; Van Kaer, Luc; Shi, Fu Dong.

In: Journal of Immunology, Vol. 175, No. 12, 15.12.2005, p. 7898-7904.

Research output: Contribution to journalArticle

Liu, R, Cava, AL, Bai, XF, Jee, Y, Price, M, Campagnolo, DI, Christadoss, P, Vollmer, TL, Van Kaer, L & Shi, FD 2005, 'Cooperation of invariant NKT cells and CD4+CD25+ T regulatory cells in the prevention of autoimmune myasthenia', Journal of Immunology, vol. 175, no. 12, pp. 7898-7904.
Liu R, Cava AL, Bai XF, Jee Y, Price M, Campagnolo DI et al. Cooperation of invariant NKT cells and CD4+CD25+ T regulatory cells in the prevention of autoimmune myasthenia. Journal of Immunology. 2005 Dec 15;175(12):7898-7904.
Liu, Ruolan ; Cava, Antonio La ; Bai, Xue Feng ; Jee, Youngheun ; Price, Mary ; Campagnolo, Denise I. ; Christadoss, Premkumar ; Vollmer, Timothy L. ; Van Kaer, Luc ; Shi, Fu Dong. / Cooperation of invariant NKT cells and CD4+CD25+ T regulatory cells in the prevention of autoimmune myasthenia. In: Journal of Immunology. 2005 ; Vol. 175, No. 12. pp. 7898-7904.
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abstract = "CD1d-restricted NKT cells and CD4+CD25+ regulatory T (Treg) cells are thymus-derived subsets of regulatory T cells that have an important role in the maintenance of self-tolerance. Whether NKT cells and Treg cells cooperate functionally in the regulation 1 of autoimmunity is not known. We have explored this possibility in experimental autoimmune myasthenia gravis (EAMG), an animal model of human myasthenia gravis, induced by immunization of C57BL/6 mice with the autoantigen acetylcholine receptor. We have demonstrated that activation of NKT cells by a synthetic glycolipid agonist of NKT cells, α-galactosylceramide (α-GalCer), inhibits the development of EAMG. α-GalCer administration in EAMG mice increased the size of the Treg cell compartment, and augmented the expression of foxp3 and the potency of CD4 +CD25+ cells to inhibit proliferation of autoreactive T cells. Furthermore, α-GalCer promoted NKT cells to transcribe the IL-2 gene and produce IL-2 protein. Depletion of CD25+ cells or neutralization of IL-2 reduced the therapeutic effect of α-GalCer in this model. Thus, α-GalCer-activated NKT cells can induce expansion of CD4 +CD25+ Treg cells, which in turn mediate the therapeutic effects of α-GalCer in EAMG. Induced cooperation of NKT cells and Treg cells may serve as a superior strategy to treat autoimmune disease.",
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