@article{96e0ab228f0a408f8c48ab6dcbd82f42,
title = "Opposing T cell responses in experimental autoimmune encephalomyelitis",
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.",
author = "Naresha Saligrama and Fan Zhao and Sikora, {Michael J.} and Serratelli, {William S.} and Fernandes, {Ricardo A.} and Louis, {David M.} and Winnie Yao and Xuhuai Ji and Juliana Idoyaga and Mahajan, {Vinit B.} and Steinmetz, {Lars M.} and Chien, {Yueh Hsiu} and Hauser, {Stephen L.} and Oksenberg, {Jorge R.} and Garcia, {K. Christopher} and Davis, {Mark M.}",
note = "Funding Information: Acknowledgements We thank members of the Davis, Chien, Garcia and Steinman laboratories for discussions. We thank A. Han and M. M. Mamedov for help designing mouse TCR primers, and V. Mallajyosulla for help with the H2-Db library constructs. We thank the Stanford Functional Genomics Facility and the Human Immune Monitoring Center for DNA and RNA sequencing (NIH shared facility equipment grant, S10OD018220). We thank C. Carswell, B. Gomez and the Stanford Shared FACS facility for assistance in sorting cells and providing access to the equipment. We also thank A. Nau, L. Steinman and C. Tato for critical reading of the manuscript and discussions. We thank C. Bohlen for myelin proteins. N.S. was supported by a Postdoctoral Fellowship from National Multiple Sclerosis Society (NMSS) and also a Career Transition Grant from NMSS. F.Z. was supported by the Ovarian Cancer Research Fund Alliances. Human samples collection was supported by a grant from NMSS RG-1611-26299 (J.R.O and S.L.H). J.I. is funded by the US National Institutes of Health (NIH) grant 1DP2AR069953. R.A.F. is supported by The Wellcome Trust for the Sir Henry Wellcome Fellowship (WT101609MA). M.M.D. and K.C.G. are funded by the US NIH (U19 AI057229) and the Howard Hughes Medical Institute. K.C.G. is also funded by the US NIH (R01AI103867) and Mathers Foundation. Additional early support also came from the Simons Foundation (to M.M.D.). Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2019",
month = aug,
day = "22",
doi = "10.1038/s41586-019-1467-x",
language = "English",
volume = "572",
pages = "481--487",
journal = "Nature",
issn = "0028-0836",
number = "7770",
}