# Distinct functions for CD8 T cells in cutaneous leishmaniasis

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $427,364

## Abstract

PROJECT SUMMARY
Cutaneous leishmaniasis is a disease caused by leishmania parasites, and exhibits a wide range of clinical
manifestations from self-healing lesions to chronic debilitating infections. Currently there are no vaccines for
this disease, and the drugs used to resolve the infections are often ineffective. Although the parasites are
important determinants of disease severity, the immune response itself causes a large amount of pathology.
CD8 T cells have been shown to play a dual role in disease by being both protective when they produce IFN-γ,
but pathogenic when they mediate inflammation-inducing cell death in lesions. We found that IFN-γ-producing
protective CD8 T cells are restricted to draining lymph nodes, whereas cytotoxic and therefore pathogenic CD8
T cells are found in leishmanial lesions in both experimental murine models of the disease and in patients. Our
preliminary results suggest that this dichotomy in CD8 T cell function is a response to the tissue
microenvironment and that protective IFN-γ-producing CD8 T cells become cytolytic once they enter
leishmanial lesions. The factors involved in this conversion are unknown, and here we propose to fill this gap in
knowledge. In our first aim we will determine how the tissue microenvironment initiates the cytolytic pathway
in CD8 T cells. We will test the role of hypoxia, IL-1β and IL-15 in promoting cytolytic T cell development and
determine how heterogeneous the CD8 T cells are within the lymph nodes and lesions. In our second aim, we
will determine what induces the expression of Blimp-1, a transcription factor that regulates cytolytic T cell
function and is required for CD8 T cell-mediated disease. In addition, we will test the ability of Blimp-1 to
promote pathology by enhancing CD8 T cell recruitment to lesions. Both of these aims will provide information
helpful in designing therapies that might block the development of pathogenic CD8 T cells. Finally, in the third
aim we will evaluate the role of neutrophils and the skin microbiota in altering the skin microenvironment. Our
preliminary results suggest that neutrophils regulate O2 levels in lesions, that the microbiota amplify neutrophil
recruitment and both neutrophils and the microbiota are required for CD8 T cell-mediated disease. Overall,
these studies will provide information from murine models that will be foundational in understanding the
immune responses mediating and regulating disease in cutaneous leishmaniasis.

## Key facts

- **NIH application ID:** 10441756
- **Project number:** 1R01AI162711-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Fernanda Novais
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $427,364
- **Award type:** 1
- **Project period:** 2022-02-07 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10441756

## Citation

> US National Institutes of Health, RePORTER application 10441756, Distinct functions for CD8 T cells in cutaneous leishmaniasis (1R01AI162711-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10441756. Licensed CC0.

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