Ashley Brate

The Role of CNS-Specific CD8+ T cells in Relapsing-Remitting Experimental Autoimmune Encephalomyelitis

Multiple Sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system characterized by the infiltration of immune cells across the blood-brain barrier. While the contribution of CD4+ T cells is well characterized in MS, the role of CD8+ T cells remains ambiguous. Studies from our lab demonstrate that CNS-specific CD8+ T cells possess a disease-ameliorating function in MS and are even protective in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Interestingly, this suppressive function of CD8+ T cells is deficient during MS relapses and is restored during quiescence, suggesting that lack of CD8+ T cell mediated regulatory function may lead to relapses in MS. My project aims to investigate this by evaluating the role of CD8+ T cells in the context of the relapsing-remitting model (RR-EAE). This includes determining whether CD8+ T cells can prevent relapses in RR-EAE and exploration of the distinct phenotypic and mechanistic features of regulatory CD8+ T cells in RR-EAE.

Boyden AW, Brate AA, Karandikar NJ. Early IFNγ-Mediated and Late Perforin-Mediated Suppression of Pathogenic CD4 T Cell Responses Are Both Required for Inhibition of Demyelinating Disease by CNS-Specific Autoregulatory CD8 T Cells. Front Immunol. 2018 Oct 9;9:2336. doi: 10.3389/fimmu.2018.02336. eCollection 2018. PubMed PMID: 30356717; PubMed Central PMCID: PMC6189364.

Brate AA, Boyden AW, Jensen IJ, Badovinac VP, Karandikar NJ. A Functionally Distinct CXCR3+/IFN-γ+/IL-10+ Subset Defines Disease-Suppressive Myelin-Specific CD8 T Cells. J Immunol. 2021 Mar 15;206(6):1151-1160. doi: 10.4049/jimmunol.2001143. Epub 2021 Feb 8. PMID: 33558376; PMCID: PMC8059448.

Itani FR, Sinha S, Brate AA, Pewe LL, Gibson-Corley KN, Harty JT, Karandikar NJ. Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen. Sci Rep. 2017 May 8;7(1):1519. doi: 10.1038/s41598-017-01771-8. PubMed PMID: 28484224; PubMed Central PMCID: PMC5431563.

Honors and Awards

  • AAI Trainee Abstract Award, 2018
  • NIH Pre-Doctoral Training Grant T32AI007485, 2017-2018
  • Graduate College Post-Comprehensive Research Award, Spring 2017
  • Ballard Seashore Fellowship – Graduate College
  • Trainee Abstract Award, to AAI Annual Meeting 2019
Associate Scientist
Cygnal Therapeutics
Ashley Brate