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

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $718,155

## Abstract

ABSTRACT
Even with successful viral control, HIV-infected individuals exhibit co-morbidities associated with older age,
including osteoporosis, stroke, dementia, and cancer. In aviremic HIV+ individuals and the general geriatric
population, age-associated diseases and mortality correlate with plasma markers of inflammation and intestinal
permeability. The gut is a major reservoir of latently HIV-infected cells, and HIV enteropathy, defined as
pathologic processes in the small intestine and colon, is a hallmark of HIV infection. Our preliminary data
implicate gamma delta T cells as an inflammatory driver in ART-suppressed HIV infection and with normal
aging. gamma delta T cells are a non-conventional T cell lineage that comprise ≤10% of circulating T cells yet are found in
considerably higher proportions in the epithelium of the intestine. Also, there is evidence that this unique T cell
population regulates intestinal barrier function during normal conditions, and that gamma delta T pro-inflammatory activity
causes damage at epithelial sites and to epithelial barriers. Therefore, we hypothesize that with virally
suppressed HIV infection and with normal aging, gastrointestinal gamma delta T cells are stimulated via directly harboring
HIV and/or exposure to inflammatory factors and this aberrant activation leads to breakdown of tight junctions of
the intestinal epithelial barrier, causing increased release of microbial products and inflammatory gamma delta T cells into
the circulation. Further, we predict that aged gamma delta T cells exhibit functional profiles skewed towards inflammatory
cytokines/cytotoxicity in response to either direct HIV infection and/or stimulatory factors. In this application, we
propose to test these hypotheses using advanced and innovative approaches, including 25-color flow cytometry,
31-color imaging mass cytometry of recto-sigmoid biopsies, 19- and 33-plex analyses of plasma and cell culture
supernatants, respectively, and multiple algorithms for multivariate analysis of collected datasets. Our
bioinformatic data analysis plan will enable identifying novel gamma delta T cell subsets and parsing the differential impacts
of age with and without HIV infection. In Aim 1 we will perform a cross-sectional study of our HIV and Aging
cohort to determine the links between circulating gamma delta T cell subsets, plasma inflammatory and intestinal
permeability markers, and intestinal architecture and cellular composition. In Aim 2 we will determine the
temporal links between gamma delta T cell subsets, plasma markers, and the onset and/or progression of geriatric
outcomes via a longitudinal study of older subjects with and without ART-suppressed HIV. In Aim 3, we will
perform in vitro assays to determine how age and HIV infection impact gamma delta T cell functions, including the capacity
to breakdown intestinal epithelial cell monolayers. We predict that our proposed experiments will identify the
biological mechanisms that drive...

## Key facts

- **NIH application ID:** 10862859
- **Project number:** 5R01AG065050-05
- **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:** $718,155
- **Award type:** 5
- **Project period:** 2020-08-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862859

## Citation

> US National Institutes of Health, RePORTER application 10862859, Gamma delta T cells promote inflammation in aviremic HIV infection and normal aging (5R01AG065050-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10862859. Licensed CC0.

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