# IFN-γ independent inhibition of MTB growth in human macrophages

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH CTR AT TYLER · 2020 · $495,150

## Abstract

It is generally believed that CD4+CD25+Foxp3+ T-cells (Tregs) inhibit effective immunity to microbial pathogens.
In humans, we and others have found increased numbers of CD4+Foxp3+ T-cells in TB patients. We also found
that in persons with latent tuberculosis infection (LTBI), Tregs expand in response to Mycobacterium.
tuberculosis (Mtb), produce TGF-β and IL-10 and inhibit IFN-γ production by CD4+ and CD8+ cells, suggesting
that they may limit tissue inflammation and destruction. However, in humans, some activated T-cells express
Foxp3 transiently and these cells lack classical regulatory function. Recently we made a surprising observation
that a subpopulation of CD4+CD25+Foxp3+ cells from persons with LTBI inhibits growth of M.tb in human
monocyte-derived macrophages (MDMs). A soluble factor, Rho GDP dissociation inhibitor (D4GDI), produced
by apoptotic CD4+CD25+ Foxp3+D4GDI+ cells is responsible for this inhibition of M.tb growth in human
macrophages and in mice. Our study provides the first evidence that a subpopulation of CD4+CD25+Foxp3+
cells enhances immunity to M. tb, and identified a novel IFN-γ independent but T-cell dependent mechanism
that inhibits M. tb growth in human macrophages. This proposal will determine the role of D4GDI in M.tb
infection through the following specific aims. Aim 1. Determine the mechanisms by which D4GDI inhibit
mycobacterial growth. Aim 2. Characterize the phenotype and function of D4GDI-producing FoxP3+ cells in
LTBI+ individuals and tuberculosis patients. Aim 3. Determine the relevance of expansion of D4GDI+Foxp3+
cells to progression of LTBI to active TB.

## Key facts

- **NIH application ID:** 9913448
- **Project number:** 5R01AI123310-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH CTR AT TYLER
- **Principal Investigator:** Ramakrishna Vankayalapati
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $495,150
- **Award type:** 5
- **Project period:** 2017-05-08 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9913448

## Citation

> US National Institutes of Health, RePORTER application 9913448, IFN-γ independent inhibition of MTB growth in human macrophages (5R01AI123310-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9913448. Licensed CC0.

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