# Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease

> **NIH VA I01** · IOWA CITY VA MEDICAL CENTER · 2020 · —

## Abstract

Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system (CNS). A
great deal of our understanding about the immunologic processes that underlie MS derives from studies in its
autoimmune animal model, experimental autoimmune encephalomyelitis (EAE). However, the vast majority of
studies in EAE and MS have focused on evaluating and targeting CD4+ T cell responses, with the general
assumption that these diseases are predominantly Th1/Th17-mediated and Th2/Treg-modulated. Recent
reports from others and us indicate that CD8+ T cells play a role in the pathogenesis as well as regulation of
autoimmune demyelination. Our recent studies in MS and EAE have provided evidence for a novel and
unexpected disease suppressive role for CNS-specific CD8+ T cells and also demonstrated the
requirement of CD8+ T cells in mediating effects of glatiramer acetate (GA) immunotherapy. Based on
our data, we hypothesize that a subset of autoantigen-specific or GA-induced CD8 T cells form an
important arm of immune regulation during autoimmune demyelinating disease. We propose that this
process can be harnessed for the development of an effective immunotherapeutic strategy. The
experiments proposed in this application will utilize EAE models to address the fundamental cellular and
molecular mechanisms of immune modulation by intrinsic and therapeutic CD8 T cells. In addition, the most
potent immune suppressive subset of these populations will be defined with the goal of developing a novel
adoptive immunotherapeutic approach. We believe that the proposed experiments will provide greater
fundamental insights into CD8 T cell-mediated immune regulation and pave the way for newer intervention
strategies for this and other immune-mediated diseases.

## Key facts

- **NIH application ID:** 9932278
- **Project number:** 5I01BX003677-04
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** NITIN J KARANDIKAR
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932278

## Citation

> US National Institutes of Health, RePORTER application 9932278, Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease (5I01BX003677-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9932278. Licensed CC0.

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