Opposing T cell responses in experimental autoimmune encephalomyelitis

Naresha Saligrama, Fan Zhao, Michael J. Sikora, William S. Serratelli, Ricardo A. Fernandes, David M. Louis, Winnie Yao, Xuhuai Ji, Juliana Idoyaga, Vinit B. Mahajan, Lars M. Steinmetz, Yueh Hsiu Chien, Stephen L. Hauser, Jorge R. Oksenberg, K. Christopher Garcia, Mark M. Davis

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Experimental autoimmune encephalomyelitis is a model for multiple sclerosis. Here we show that induction generates successive waves of clonally expanded CD4+, CD8+ and γδ+ T cells in the blood and central nervous system, similar to gluten-challenge studies of patients with coeliac disease. We also find major expansions of CD8+ T cells in patients with multiple sclerosis. In autoimmune encephalomyelitis, we find that most expanded CD4+ T cells are specific for the inducing myelin peptide MOG35–55. By contrast, surrogate peptides derived from a yeast peptide major histocompatibility complex library of some of the clonally expanded CD8+ T cells inhibit disease by suppressing the proliferation of MOG-specific CD4+ T cells. These results suggest that the induction of autoreactive CD4+ T cells triggers an opposing mobilization of regulatory CD8+ T cells.

Original languageEnglish
Pages (from-to)481-487
Number of pages7
JournalNature
Volume572
Issue number7770
DOIs
StatePublished - Aug 22 2019
Externally publishedYes

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  • Cite this

    Saligrama, N., Zhao, F., Sikora, M. J., Serratelli, W. S., Fernandes, R. A., Louis, D. M., Yao, W., Ji, X., Idoyaga, J., Mahajan, V. B., Steinmetz, L. M., Chien, Y. H., Hauser, S. L., Oksenberg, J. R., Garcia, K. C., & Davis, M. M. (2019). Opposing T cell responses in experimental autoimmune encephalomyelitis. Nature, 572(7770), 481-487. https://doi.org/10.1038/s41586-019-1467-x