# Control of Humoral and Cellular Immunity to Viral Infections of the Lung by Follicular CD8 T Cells

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $490,142

## Abstract

Immunity to viral infections of the lung require cooperation between humoral and cellular arms of the immune
system. A newly defined subset of CD8 T cell, called CXCR5+ CD8 T cells, have been identified. CXCR5+ CD8
T cells can gain access to the B cell follicle of lymph nodes and interact with B cells. In settings of chronic
infection these CXCR5+ CD8 T cells may have stem-like potential and can differentiate further into effector CD8
T cells. Therefore, CXCR5+ CD8 T cells may have unique polyfunctionality to control both humoral and cellular
arms of the immune system. However, a fundamental understanding of the functions of CXCR5+ CD8 T cells
is lacking due to a paucity of tools to study these cells in vivo. The object of the proposed studies is to elucidate
the precise roles of CXCR5+ CD8 T cells in regulating cellular and antibody mediated anti-viral immunity during
acute respiratory infections, and to assess intrinsic and extrinsic mechanisms controlling these functions. We
hypothesize that polyfunctional CXCR5+ CD8 T cells restrain humoral immunity yet are essential for cellular
immunity and T cell memory. We also hypothesize that the immune system can fine-tune immunity by altering
CXCR5+ CD8 T cell fates through extrinsic signals from effector Tfh cells, and intrinsic factors such as the
expression of the transcription factor Tbet. To test these hypotheses, we will: 1) assess the roles of CXCR5+
CD8 T cells to control humoral and cellular immunity at distinct times in vivo during viral infection and vaccination
with Influenza and SARS-CoV-2, and 2) assess the roles of extrinsic signals from Tfh cells and intrinsic signals
from Tbet to control CXCR5+ CD8 T cell memory and polyfunctionality. We will pursue these aims using
innovative strategies to identify and perturb CXCR5+ CD8 T cell subsets in vivo during viral infection and
vaccination in intact, polyclonal, mice. These strategies include newly developed CXCR5+ CD8 T cell deleter
and Tfh cell deleter models which facilitate the assessment of functionality during the distinct stages of viral
infection and vaccination. The expected outcome of these studies is an elucidation of the precise functions of,
and mechanisms controlling, CXCR5+ CD8 T cell regulation of humoral and cellular immunity. These studies
are significant because they will lead to a deeper understanding of how the immune system mediates anti-viral
immunity and will provide framework for the development of new therapeutics to enhance anti-viral immunity and
promote vaccine efficacy to influenza and SARS-CoV-2.

## Key facts

- **NIH application ID:** 10180360
- **Project number:** 1R01AI158413-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Peter The Sage
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $490,142
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180360

## Citation

> US National Institutes of Health, RePORTER application 10180360, Control of Humoral and Cellular Immunity to Viral Infections of the Lung by Follicular CD8 T Cells (1R01AI158413-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10180360. Licensed CC0.

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