# The impact of HIV driven T cell immune activation in angiogenic CD8 T cell function: the role of PAR1 signaling

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2020 · $385,698

## Abstract

SUMMARY
 HIV infected patients have twice the risk of cardiovascular disease relative to the general population. The
main drivers of cardiovascular events in patients with HIV infection are associated with chronic immune
activation, systemic inflammation and endothelial dysfunction. The molecular pathways linking HIV-driven
chronic T immune activation, vascular inflammation and increased risk of cardiovascular disease are largely
unknown. In this proposal, we will investigate the underlying mechanisms driving vascular
inflammation/damage during HIV infection by focusing in the function of angiogenic CD8 T cells (CD8 Tangs).
Under physiological conditions, Tang cells play a role in endothelial repair by promoting differentiation and
proliferation of endothelial progenitors at the site of vascular injury. The mechanisms involved in CD8 Tang cell
subset differentiation and function are not well defined. We hypothesize that HIV infection drives immune
activation of CD8 Tang cells and impairs their ability to promote vascular repair and, the chronic interference of
this pathway contributes to vascular inflammation and/or risk. In this proposal we will: 1) Identify the molecular
pathways involved in the differentiation and function of CD8 Tang cells and the role of PAR1 signaling in this
pathway. 2) Identify the impact of HIV driven T cell immune activation in CD8 Tang cell differentiation and/or
function and evaluate its relationship with cardiovascular risk/disease in patients with HIV infection. 3)
Mechanistically, in a murine model of LCMV infection, we will evaluate the role memory (tissue resident and
circulating) CD8 T cells to undergo CD8 Tang cell differentiation and determine the impact of PAR1 deficiency in
vascular repair and cardiovascular disease progression. These studies will establish the mechanisms of CD8
Tang differentiation and function in health and HIV infection. In addition, these studies will identify new molecular
targets to restore CD8 Tang function in patients. This research will have wide application in multiple
inflammatory diseases in which systemic inflammation is associated with cardiovascular risk.
.

## Key facts

- **NIH application ID:** 9933770
- **Project number:** 5R01AI145549-02
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Marta L. Catalfamo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,698
- **Award type:** 5
- **Project period:** 2019-05-23 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933770

## Citation

> US National Institutes of Health, RePORTER application 9933770, The impact of HIV driven T cell immune activation in angiogenic CD8 T cell function: the role of PAR1 signaling (5R01AI145549-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9933770. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*