# Gamma delta T cells promote inflammation in aviremic HIV infection and normal aging

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $412,500

## Abstract

PROJECT SUMMARY/ABSTRACT
There is mounting evidence of peripheral inflammation coincident with Alzheimer’s disease (AD), yet the drivers
and specific features of these immune aberrancies are unknown. Also, the connections between this peripheral
inflammation and the onset and progression of dementias are not elucidated. Our previous work found that TIGIT
expression on γδ T cells, a unique ‘innate-like’ T cell population, correlates with plasma markers of general
inflammation in both ART-suppressed HIV infection and with normal aging and may indicate a hyper-
inflammatory state of this T cell subset. γδ T cells have recently been implicated as drivers of AD pathogenesis.
The Aims of my ongoing R01 award seek to define γδ T cell subset heterogeneity in our HIV and Aging cohort
participants and to address our hypothesis that with aging and HIV infection, GI resident γδ T cells become
aberrantly activated and cause gut leakiness, resulting in an influx of immune cells and bacterial products to the
bloodstream which consequents in systemic inflammation and age-associated co-morbidities. GI abnormalities,
including microbiota dysbiosis and intestinal barrier permeability, are now strongly linked to neuroinflammation,
breakdown of the blood brain barrier (BBB), cognitive deficits, and AD. Therefore, as an addendum to the work
proposed in my R01, we propose to expand our sample analysis to include peripheral blood and brain tissue
samples from the Health Outreach Program for the Elderly (HOPE) study samples, a cohort of the NIH-funded
Boston University Alzheimer’s Disease Research Center (ARDC), to build evidence in support of our hypothesis
that with aging in some individuals, alterations in the GI tract induce resident γδ T cells into a hyperinflammatory
state, driving gut leakiness, which results in γδ T cell influx into the circulation, systemic inflammation, and
ultimately infiltration of γδ T cells and other immune components into the brain, initiating the pathogenic events
that lead to AD. We propose two Aims that will examine immune cell signatures in PBMC via 32-color spectral
flow cytometry, measurement of 30 markers of inflammation, neuroinflammation, and gut leakiness in plasma,
and 40-marker analysis of cell signatures in brain tissue from neurotypical, mild cognitively impaired, and AD
individuals. Both cross-sectional (Aim 1) and longitudinal (Aim 2) studies will be performed, with the latter
enabling cause-and-effect/mechanistic insights to be gleaned via intra-individual analysis of temporally linked
trajectories readout trajectories. Using bioinformatic platforms for data analysis, our proposed Aims will elucidate
specific links between immune signatures and temporal trajectories with the onset and progression of
neurological disease and determine connections between γδ T cells, gut leakiness, and AD. Also, our findings
will provide the Preliminary Data for an AD-related R01 application and also may elucidate novel biomarkers for
early ...

## Key facts

- **NIH application ID:** 10939760
- **Project number:** 3R01AG065050-05S1
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Jennifer E Snyder-Cappione
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $412,500
- **Award type:** 3
- **Project period:** 2020-08-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10939760

## Citation

> US National Institutes of Health, RePORTER application 10939760, Gamma delta T cells promote inflammation in aviremic HIV infection and normal aging (3R01AG065050-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10939760. Licensed CC0.

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