# Macaque T cell signatures of Mtb control

> **NIH NIH U19** · EMORY UNIVERSITY · 2020 · $251,757

## Abstract

How a majority of those infected with Mycobacterium tuberculosis (Mtb) control the infection in a state 
referred to as latent TB infection (LTBI), is not completely understood. LTBI can reactivate to clinical TB in 
some individuals. Antigen-specific T cell responses, particularly CD4+ responses, are crucial to the control 
of Mtb infection in patients as well as in primate experimentally infected with Mtb. However, the identity of 
specific T cell responses that direct the control of Mtb in the LTBI state, or are responsible for reactivation, is 
not yet understood. In this project, we propose to identify the immune signatures associated with control of 
Mtb infection as LTBI either spontaneously or upon therapy, in rhesus macaques, a model in which LTBI 
can reproducibly be induced. The objectives of project 3 are highly complementary to those of the other two 
projects within this TBRU application, but will pave the way for testing novel therapeutic avenues in the 
future. The project will generate detailed data to demonstrate that Mtb-specific T cell responses associated 
with chemotherapy-mediated bacterial clearance are distinct from persistent Mtb infection in terms of 
phenotype, function and activation, both ex vivo and in vivo. In addition, clearance of Mtb or its failure will be 
tested via reactivation with co-infection with simian immunodeficiency virus (SIV), as a model of HIV/Mtb a 
common clinical occurrence in many parts of the developing world. T cell responses noted in the same 
monkey before and after chemotherapy induced latency will also be compared and these profiles will then 
be compared with human profiles from untreated and chemotherapy treated humans derived from projects 1 
and 2. Finally, the impact of reexposure of LTBI monkeys to a heterologous Mtb will be modeled to monitor 
the evolution of specific T cell signatures in monkeys maintaining LTBI status vs those who develop clinical 
Tb, in efforts to validate the T cell signatures associated with LTBI status. Project 3 will be a collaboration 
between the Tulane and Yerkes National primate Research Centers. The studies will also markedly improve 
the definition of Mtb antigens, epitopes and their restricting MHCs in the Indian rhesus macaque, a critical 
model to address future experimental vaccines and therapies for which this project will provide correlates.

## Key facts

- **NIH application ID:** 9989020
- **Project number:** 5U19AI111211-07
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Jyothi Rengarajan
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $251,757
- **Award type:** 5
- **Project period:** 2014-08-11 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989020

## Citation

> US National Institutes of Health, RePORTER application 9989020, Macaque T cell signatures of Mtb control (5U19AI111211-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989020. Licensed CC0.

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