# Viral impact on autoimmune T cells

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $194,213

## Abstract

IL-17 producing T cells have been implicated in the pathogenesis of numerous autoimmune
diseases including multiple sclerosis. Autoimmune diseases frequently exhibit a cyclical pattern,
with periods of quiescent disease followed by exacerbations or flares. The unpredictable onset of
disease flares makes it difficult to balance the risk of more effective therapies (which come with
significant side-effects) versus the risk of long-term disability that comes with each disease
exacerbation. Hence, understanding the mechanisms that trigger flares is a critical unmet need.
Recent viral infection is one of the most common clinically associated triggers for autoimmune
disease flare. However, this presents a conundrum: viral infection drives a strong interferon
response that is known to suppress the induction of a type-17 response. In fact, IFNb is one of
the oldest and most widely-use therapies for MS, and successful therapy correlates with reduced
Th17 cells in peripheral blood. Similarly, suppression of type-17 responses is thought to contribute
to susceptibility of recently influenza-infected lungs to secondary bacterial infections. However,
there is a paucity of data on how viral infection directly impacts existing type-17 cells: either innate-
type gdT17 that provide immediate defense against bacteria amplify inflammation, or autoimmune
memory Th17 cells that can trigger relapse. Our surprising new data prompts our hypothesis that
viral infection causes transient loss of bystander type-17 cells, and that subsequent rebound of
self-reactive Th17 cells contributes to autoimmune flare. If correct, this explains one mechanism
underlying the perplexing connections between viral infection, acute susceptibility to secondary
bacterial infection and later post-viral susceptibility to autoimmune disease flare. This hypothesis
will be tested in the following specific aims: Aim 1: Determine fate of autoreactive Th17 and
bystander resident IL-17+ cells during viral infection Aim 2: Define role of autoimmune Th17 cell
reactivation by viral infection in EAE relapse susceptibility. These data will define for the first time
the impact and consequences of viral infection on existing IL-17 producing T cells and
autoimmune disease flare.

## Key facts

- **NIH application ID:** 10317311
- **Project number:** 1R21AI164732-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** John F Alcorn
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $194,213
- **Award type:** 1
- **Project period:** 2021-06-18 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317311

## Citation

> US National Institutes of Health, RePORTER application 10317311, Viral impact on autoimmune T cells (1R21AI164732-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10317311. Licensed CC0.

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