# Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease

> **NIH VA I01** · IOWA CITY VA MEDICAL CENTER · 2021 · —

## 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 studies in MS and EAE have provided evidence for a novel and
unexpected disease suppressive role for CNS-specific CD8+ T cells (CNS-CD8). Based on our data, we
hypothesize that specific functional and phenotypic subsets of CNS-CD8 form an important and
exploitable arm of immune regulation during autoimmune demyelinating disease. We propose that this
process can be harnessed for the development of effective immunotherapeutic approaches. The
experiments proposed in this application will utilize EAE models to address the fundamental cellular and
molecular mechanisms of immune modulation (IFNγ and its receptor, trafficking and cytotoxicity, suppression
at the site of pathology) by these autoregulatory CD8 T cells, and to define a potent and enhanceable immune
suppressive subset of CNS-CD8. Further, a novel vaccination strategy that reliably engages disease-reversing
CNS-CD8 will also be investigated as a proof of principle. We believe that achievable results from the
proposed experiments will provide greater fundamental insights into CD8 T cell-mediated immune regulation
and pave the way for newer intervention strategies for MS and other immune-mediated diseases.

## Key facts

- **NIH application ID:** 10248844
- **Project number:** 2I01BX003677-05
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** NITIN J KARANDIKAR
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2017-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248844

## Citation

> US National Institutes of Health, RePORTER application 10248844, Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease (2I01BX003677-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10248844. Licensed CC0.

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