# Defining the Role of Molecules Unique to Encephalitogenic T Cells in MS

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2021 · $390,000

## Abstract

Specific Aims
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) that affects
an estimated 1 million Americans1. The cause of MS is unknown, there is no cure, and the current therapies have limited
efficacy. My laboratory focuses on identifying molecules critical to the pathogenicity of encephalitogenic T cells. Since
the CNS is an immune-privileged tissue and immunological surveillance is limited, we hypothesize that encephalitogenic
T cells express unique molecules that enhance their encephalitogenic capacity, which are distinct from the CD4 T cells
that protect us from infection, and that these molecules may be therapeutic targets for MS. The goal of this study is to
identify molecular targets in encephalitogenic effector CD4 T cells that could be therapeutically manipulated to minimize
the differentiation of encephalitogenic T cells, as well as extinguish or anergize established encephalitogenic T cells,
while sparing pathogen-specific CD4 T cells. We hypothesize that encephalitogenic T cells, regardless of whether they are
Th1 or Th17, share specific molecular pathways that can be therapeutically targeted to halt progression of CNS
autoimmunity. Aim 1: Determine the role of genes differentially expressed in both encephalitogenic Th1 and Th17 cells.
Aim 2: Analyze the validity of encephalitogenic molecules as MS-specific therapeutic targets with minimal immune
compromise. The role that these encephalitogenic-associated molecules play in the generation and/or function of
encephalitogenic T cells will be determined in both mouse and human CD4 T cells, as well as whether there is a
differential role of these molecules in pathogenic versus protective T cells. Many studies have focused on the
differentiation of encephalitogenic T cells, but far fewer studies have analyzed the unique characteristics of
encephalitogenic effector/memory T cells in MS. This data will help identify therapeutic targets in newly differentiating
encephalitogenic T cells to limit the generation of potentially pathogenic T cells in MS. Importantly, this study will also
identify molecules that are critical to the function of encephalitogenic effector/memory CD4 T cells that may be
contributing to disease progression and may be less vulnerable to therapies that target T cell differentiation or specific T
cell subsets. This study is novel in that the focus is on T cell encephalitogenicity, irrespective of whether the T cells have
a Th1 or Th17 phenotype. Furthermore, this study will compare protective versus pathogenic CD4 T cell responses in MS
patients to identify therapeutic targets that would not compromise protection to infections.

## Key facts

- **NIH application ID:** 10227187
- **Project number:** 5R01AI140741-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Amy E Lovett-Racke
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2019-09-04 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227187

## Citation

> US National Institutes of Health, RePORTER application 10227187, Defining the Role of Molecules Unique to Encephalitogenic T Cells in MS (5R01AI140741-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10227187. Licensed CC0.

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