# Immunoregulatory and effector roles of natural killer cell subsets

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $463,328

## Abstract

PROJECT SUMMARY
We propose to build upon exciting preliminary data highlighting unique effects natural killer (NK) cell subsets
can have on regulating T cell responses using preclinical models of hematopoietic stem cell transplantation
(HSCT), viral resistance, and cancer. While NK cells have been delineated into various subsets, the role of
these subpopulations in viral and cancer resistance is unclear. We have built on numerous reports indicating
that licensing or arming of the subsets based on MHC recognition gives rise to the various immunoregulatory
functions they can exert on immune responses. We have found licensed and unlicensed NK cells to
differentially affect T cell immune responses during viral infection and cancer acting as “helper” and
“suppressor” populations. This proposal will seek to delineate the mechanisms underlying these effects on
each other and T cells, assess the impact of HSCT and the role of the subsets in the context of
cytomegalovirus infection and finally to link several species with regard to a molecular signature correlating
with the subset phenotypes. Our first aim will build on this data and investigate the different mechanisms that
NK cells can use to impact T cell responses during viral infection. The second aim will build on this concept of
differential effects of NK subsets, but now examine how the immune environment established following HSCT
can alter the effector roles observed as well as impact T cell recovery. The final aim will determine the impact
CMV can have on NK subset reconstitution using both mouse and non-human primate models of autologous
HSCT. This aim will also assess the impact of CMV on potential graft-versus-leukemia (GVL) effects following
HSCT. Importantly, throughout the three aims, we will molecularly compare licensed and unlicensed NK cell
subsets from multiple species including mouse, human, and non-human primate to link the common attributes
of the subsets.

## Key facts

- **NIH application ID:** 10074587
- **Project number:** 5R01HL140921-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** WILLIAM JOSEPH MURPHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $463,328
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074587

## Citation

> US National Institutes of Health, RePORTER application 10074587, Immunoregulatory and effector roles of natural killer cell subsets (5R01HL140921-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10074587. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*