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

Description: PROJECT NARRATIVE In individuals with HIV infection, chronic inflammation is present even with undetectable viral loads, and such persons often present with co-morbidities associated with older age, including bone loss, cancers, stroke, cardiovascular disease, and dementia. In this application, we propose to test the hypothesis that gamma delta T cells, a unique ‘innate-like’ T cell subset, exhibit hyper-inflammatory activity in the gastrointestinal tract of aviremic HIV+ individuals and uninfected older subjects, and this aberrant activation directly causes increased permeability of intestinal epithelium, leading to movement of GI microbial products and inflammatory gamma delta T cells into the circulation, which spurs and propagates systemic inflammation. Identification of the mechanisms driving increased intestinal permeability with aviremic HIV infection and normal aging is critical to develop novel therapeutic strategies to abrogate and/or prevent age-associated co-morbidities.

Funder: National Institutes of Health

Amount: $718,200

Funding type: research

Funder scheme: R01

Start date: 2020-08-15

End date: 2026-05-31

Investigator: JENNIFER E SNYDER-CAPPIONE

Institution: BOSTON UNIVERSITY MEDICAL CAMPUS