Opposing T cell responses in experimental autoimmune encephalomyelitis

  • Nature. 2019 Aug;572(7770):481-487. doi: 10.1038/s41586-019-1467-x.
Naresha Saligrama  1  2 ,  Fan Zhao  #  1 ,  Michael J Sikora  #  3 ,  William S Serratelli  2 ,  Ricardo A Fernandes  4 ,  David M Louis  2 ,  Winnie Yao  2 ,  Xuhuai Ji  5 ,  Juliana Idoyaga  1 ,  Vinit B Mahajan  6  7 ,  Lars M Steinmetz  3  8  9 ,  Yueh-Hsiu Chien  1  2  10 ,  Stephen L Hauser  11 ,  Jorge R Oksenberg  11 ,  K Christopher Garcia  4  12  13 ,  Mark M Davis  14  15  16
Affiliations
  • 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. [email protected].
  • 15. Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
  • 16. The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
  • # Contributed equally.
PMID: 31391585 DOI: 10.1038/s41586-019-1467-x
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.

Products