# Mechanisms of iNKT cell anti-viral adjuvancy

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $382,500

## Abstract

Summary:
Invariant natural killer T (iNKT) cells have been shown to promote resistance to a variety of viral infections.
Despite their cytopathic-sounding name, it does not seem that the anti-viral effects of iNKT cells are due to
their killing of infected cells. Instead, iNKT cells function as "cellular adjuvants" that promote anti-viral
responses by other lymphocytes, including antigen-specific T cells. iNKT cells are an innate T cell population
that is present in all individuals, and that utilizes a conserved TCR that recognizes lipid "patterns" presented by
non-polymorphic CD1d molecules. As a result of these features, iNKT cells can be targeted in genetically
diverse human populations using a single therapeutic strategy (e.g. anti-TCR antibodies, synthetic lipid
antigens). Thus, iNKT cells could be exploited as a generic (i.e. HLA-independent) strategy to promote anti-
viral antigen-specific T cell responses. The goal of this project is to provide mechanistic data that will support
the development of human iNKT cells as broad anti-viral agents. The mechanisms involved in human iNKT-
mediated adjuvancy in vivo will be investigated using a model of Epstein-Barr virus infection, in which
autologous T cells control the degree of virally-driven B cell hyperplasia. Our preliminary studies show that
administering iNKT cells at late time points after viral infection is associated with clearance of B-
lymphoproliferative masses and with enhanced antigen-specific T cell responses. We will investigate two
specific hypotheses about the mechanisms by which iNKT cells mediate these effects: i) by conditioning of
monocytic APCs in a way that diminishes their immunosuppressive properties and/or enhances their
immunostimulatory features; ii) by directly activating T cells in a way that enables them to overcome
suppressive signals. Aim1 will determine iNKT cell activation requirements; Aim 2 will ascertain the
importance of iNKT cell interactions with monocytic APCs; Aim 3 will assess the impact of iNKT cells on T
cells. These studies will significantly advance our understanding of the cellular and molecular pathways
involved in iNKT-mediated adjuvancy, and will thus guide the development of clinical strategies to engage
iNKT cells to promote anti-viral immunity.

## Key facts

- **NIH application ID:** 10215435
- **Project number:** 5R01AI136500-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Jenny E. Gumperz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2018-08-07 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215435

## Citation

> US National Institutes of Health, RePORTER application 10215435, Mechanisms of iNKT cell anti-viral adjuvancy (5R01AI136500-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10215435. Licensed CC0.

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