# Alternative functions for gamma delta T cells in the  immune response to Mycobacterium

> **NIH NIH P20** · UNIVERSITY OF KANSAS LAWRENCE · 2020 · $128,576

## Abstract

PROJECT SUMMARY 
 Mycobacterium bovis is a member of the M. tuberculosis complex and the causative agent of tuberculosis 
(TB) in cattle and zoonotic infections in humans. Bovine TB is an excellent model for understanding TB in 
humans, as the diseases are parallel in many aspects of pathogenesis and innate and adaptive immune 
responses. Further, the study of bovine and human TB exemplifies the One Health approach as discoveries in 
both species have been closely intertwined throughout history. γδ T cells are a set of non-conventional CD3+ T 
cells that share important characteristics of both the innate and adaptive arms of the immune system. γδ T 
cells are particularly recognized for their ability to respond robustly to Mycobacterium infection. Several 
characteristics of γδ T cells, predominantly those functions commonly shared with αβ T cells, such as IFNγ 
production have been identified and characterized. However, it is increasingly apparent that γδ T cells have the 
capacity for a diverse array of immune functions including chemokine production, antigen presentation and 
regulatory cytokine production. These alternative immune functions are not well described in the context of TB 
infection and their role in vivo, particularly at the site of infection, remains poorly defined. Aim 1 of the proposed 
project employs a novel γδ T cell-alveolar macrophage co-culture system to model interactions that occur 
between immune populations at the site of M. bovis infection in the lungs. Next-generation RNA-Sequencing 
and transcriptome analysis will be performed on samples from the co-culture system to identify novel and 
alternative functions for γδ T cells responding to Mycobacterium infection. γδ T cells are hypothesized to play a 
critical role in granuloma formation and immune cell recruitment; however, given the difficulty of studying the 
immune response to TB in vivo, little is known about their capacity to promote improved disease outcome 
during TB infection. Therefore, Aim 2 proposes to utilize RNAScope, a commercial technology similar to in situ 
hybridization to identify local γδ T cell responses that correlate with increased resistance to infection, or 
improved outcome during TB. If successful, the RNA-Seq analysis in Aim 1 will further inform studies of γδ T 
cell functions in infected tissues. The proposed studies will be amongst the first to correlate γδ T cell responses 
in the peripheral blood, with those that occur in the local tissues during M. bovis infection. Effectively engaging 
γδ T cells in vaccine-induced protection from TB is expected to enhance the efficacy of candidate TB vaccines. 
Aim 3 proposes to test two vaccine platforms that specifically target unique γδ T cell-specific pattern 
recognition receptors, to determine if these platforms effectively engage γδ T cells in vaccine-induced immunity 
to TB. The knowledge gained from these studies will contribute to our understanding of the basic biology of γδ 
T cells an...

## Key facts

- **NIH application ID:** 9994335
- **Project number:** 5P20GM103638-09
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Jodi L. McGill
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $128,576
- **Award type:** 5
- **Project period:** 2017-07-15 → 2018-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994335

## Citation

> US National Institutes of Health, RePORTER application 9994335, Alternative functions for gamma delta T cells in the  immune response to Mycobacterium (5P20GM103638-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9994335. Licensed CC0.

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