# Tricytotoxic T cells protect against intracellular infection in human skin

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $72,038

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal describes a five-year mentored training program for the career development of a physician-
scientist to examine how cellular cytotoxicity mediates host defense to intracellular pathogens in human skin.
To study this the disease leprosy, caused by intracellular infection with M. leprae, will be utilized as a model.
Currently, it is thought that the antimicrobial immune response in resistant T-lep vs. susceptible L-lep is
conferred in large part by cytotoxic T lymphocytes (CTL). CTLs, however, are heterogeneous such that the
key T cell population that contributes to host defense is unknown. Here we propose to study a newly identified
population of CTLs which co-express granzyme B (GZMB), perforin (PRF) and granulysin (GNLY), termed
`tricytotoxic' (T-CTL) and posit that this CTL population contributes to host defense against M. leprae. Using
high throughput RNA sequencing coupled with functional studies this proposal will investigate the breadth and
mechanism of the cytotoxic T cell response to an infectious agent in human skin including: Aim 1) Determine
molecular markers that define the T-CTL subset, and ascertain the functional relevance of T-CTL in
host defense at the site of disease, and Aim 2) Identify the mechanisms that differentiate, expand, and
functionally regulate T-CTL. This approach directly addresses several goals of NIAMS as outlined in the
“Immunobiology and Immune Diseases of Skin Program” including regulation of skin immune responses by T
cells and the characterization of the soluble mediators they express including antimicrobial peptides in a
human skin disease. The candidate previously completed a PhD studying how adaptive immunity may be
shaped to mutating pathogens and has completed clinical residency in dermatology, clinical fellowship in
dermatopathology as well as post-doctoral fellowship training through the STAR program research track at
UCLA. This proposal will afford him the ability to develop an understanding of a completely human system for
research permitting the expansion of clinical translational skills due to the large component of leprosy patients
and healthy controls. Additionally he will develop new molecular techniques including high throughput RNA
sequencing and the skill set required to analyze such data. Outcomes from this research along with the newly
developed skill sets will be widely applicable to the study of any skin disorder. This critical mentored phase of
training will be guided by Robert Modlin, MD, an expert in the fields of leprosy, immunology, and translational
cutaneous medicine who has successfully trained numerous independent investigators. In total, this research
will have far reaching implications for understanding how the immune system in general protects against
infections, providing new avenues for exploration towards to the goal of immune based therapies. This
program will allow the candidate to develop the skills and tools needed to embark upon t...

## Key facts

- **NIH application ID:** 9869856
- **Project number:** 5K08AR074552-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Samuel Jackson Balin
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $72,038
- **Award type:** 5
- **Project period:** 2019-02-11 → 2020-07-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869856

## Citation

> US National Institutes of Health, RePORTER application 9869856, Tricytotoxic T cells protect against intracellular infection in human skin (5K08AR074552-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9869856. Licensed CC0.

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