# T Lymphopenia in Ischemic Heart Failure

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2024 · $376,421

## Abstract

Myocardial infarction (MI)-induced heart failure is the leading cause of morbidity and mortality in the United
States. About one in four MI patients will progress to develop chronic heart failure, which has a 5-year mortality
rate of 40%. It is highly urgent to improve long-term outcomes of MI patients. Lymphopenia, a reduction in
peripheral blood lymphocyte count (primarily due to T-cell loss), has consistently been shown to correlate with
worse cardiac function and poor outcome in MI patients and is an independent marker to predict the prognosis.
Unfortunately, how T lymphopenia occurs following MI and whether targeting T lymphopenia has therapeutic
potential are largely unknown. Using the mouse MI-induced ischemic heart failure model, our preliminary data
showed that MI-induced T lymphopenia may involve blood T-cell redistribution to the bone marrow and T cell
development impairment. CD4+ T-cell activation is known to improve wound healing post-MI. Thus, persistent
CD4+ T lymphopenia may reduce protective CD4+ T-cell response and compromise myocardial repair after MI.
The goals of this proposal are: 1) to elucidate the underlying mechanisms that cause T lymphopenia following
MI; and 2) to investigate whether inhibiting CD4+ T lymphopenia can serve as a therapeutic strategy. We
hypothesize that MI induces T lymphopenia by both stimulating T-cell trafficking from blood to the bone marrow
and impairing T lymphopoiesis; inhibiting CD4+ T lymphopenia improves post-MI cardiac repair. Three specific
aims will address this novel hypothesis in a mouse ischemic heart failure model that combines multidisciplinary
approaches. Specific Aim 1 will examine the mechanisms of blood T-cell trafficking to the bone marrow and
alterations of distinct T-cell phenotypes and functions after MI. Specific Aim 2 will determine the mechanisms by
which MI impairs T lymphopoiesis. Specific Aim 3 will examine the hypothesis that inhibiting CD4+ T lymphopenia
would improve post-MI cardiac repair. Accomplishment of this proposal will provide new insights into T
lymphopenia mechanisms in ischemic heart failure and may offer potential intervention strategies to improve the
prognosis of heart failure patients.

## Key facts

- **NIH application ID:** 10880433
- **Project number:** 5R01HL164446-03
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Yonggang Ma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $376,421
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880433

## Citation

> US National Institutes of Health, RePORTER application 10880433, T Lymphopenia in Ischemic Heart Failure (5R01HL164446-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10880433. Licensed CC0.

---

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