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Nature. 2019 Aug 7. doi: 10.1038/s41586-019-1467-x. [Epub ahead of print]

Opposing T cell responses in experimental autoimmune encephalomyelitis.

Author information

1
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
2
Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
3
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
4
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
5
Human Immune Monitoring Center, Stanford University School of Medicine, Stanford, CA, USA.
6
Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, CA, USA.
7
Veterans Affairs Palo Alto Health Care, Palo Alto, CA, USA.
8
Stanford Genome Technology Center, Stanford University, Palo Alto, CA, USA.
9
European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
10
Program in Immunology, Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
11
Department of Neurology and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
12
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
13
The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
14
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA. mmdavis@stanford.edu.
15
Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA. mmdavis@stanford.edu.
16
The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA. mmdavis@stanford.edu.

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.

PMID:
31391585
DOI:
10.1038/s41586-019-1467-x

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