The disease-ameliorating function of autoregulatory CD8 T cells is mediated by targeting of encephalitogenic CD4 T cells in experimental autoimmune encephalomyelitis

Sterling B. Ortega, Venkatesh P. Kashi, Andrew F. Tyler, Khrishen Cunnusamy, Jason P. Mendoza, Nitin J. Karandikar

Research output: Contribution to journalArticle

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Abstract

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS, and CD8 T cells are the predominant T cell population in MS lesions. Given that transfer of CNS-specific CD8 T cells results in an attenuated clinical demyelinating disease in C57BL/6 mice with immunization-induced experimental autoimmune encephalomyelitis (EAE), we investigated the cellular targets and mechanisms of autoreactive regulatory CD8 T cells. In this study we report that myelin oligodendrocyte glycoprotein peptide (MOG35-55)-induced CD8 T cells could also attenuate adoptively transferred, CD4 T cell-mediated EAE. Whereas CD8-/- mice exhibited more severe EAE associated with increased autoreactivity and inflammatory cytokine production by myelin-specific CD4 T cells, this was reversed by adoptive transfer of MOG-specific CD8 T cells. These autoregulatory CD8 T cells required in vivo MHC class Ia (KbD b) presentation. Interestingly, MOG-specific CD8 T cells could also suppress adoptively induced disease using wild-type MOG35-55-specific CD4 T cells transferred into KbDb-/- recipient mice, suggesting direct targeting of encephalitogenic CD4 T cells. In vivo trafficking analysis revealed that autoregulatory CD8 T cells are dependent on neuroinflammation for CNS infiltration, and their suppression/cytotoxicity of MOG-specific CD4 T cells is observed both in the periphery and in the CNS. These studies provide important insights into the mechanism of disease suppression mediated by autoreactive CD8 T cells in EAE.

Original languageEnglish (US)
Pages (from-to)117-126
Number of pages10
JournalJournal of Immunology
Volume191
Issue number1
DOIs
StatePublished - Jul 1 2013

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Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Demyelinating Diseases
Multiple Sclerosis
Myelin-Oligodendrocyte Glycoprotein
Adoptive Transfer
Regulatory T-Lymphocytes
Myelin Sheath
Inbred C57BL Mouse
Immunization

ASJC Scopus subject areas

  • Immunology

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The disease-ameliorating function of autoregulatory CD8 T cells is mediated by targeting of encephalitogenic CD4 T cells in experimental autoimmune encephalomyelitis. / Ortega, Sterling B.; Kashi, Venkatesh P.; Tyler, Andrew F.; Cunnusamy, Khrishen; Mendoza, Jason P.; Karandikar, Nitin J.

In: Journal of Immunology, Vol. 191, No. 1, 01.07.2013, p. 117-126.

Research output: Contribution to journalArticle

Ortega, Sterling B. ; Kashi, Venkatesh P. ; Tyler, Andrew F. ; Cunnusamy, Khrishen ; Mendoza, Jason P. ; Karandikar, Nitin J. / The disease-ameliorating function of autoregulatory CD8 T cells is mediated by targeting of encephalitogenic CD4 T cells in experimental autoimmune encephalomyelitis. In: Journal of Immunology. 2013 ; Vol. 191, No. 1. pp. 117-126.
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