# Project 3: NK and T cell cooperation in CMV infection

> **NIH NIH P01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $8,562

## Abstract

Human cytomegalovirus (HCMV) is the most common cause of congenital viral infection and an
important cause of morbidity and mortality following solid organ and hematopoietic cell
transplantation. Understanding how the immune system responds to HCMV is vital to the efforts
to achieve efficient eradication of infection. This proposal aims to identify novel relationships
between NK cells and T cells during HCMV infection, with the central hypothesis that a strong T
cell response to HCMV infection can abrogate the emergence of an adaptive NK “memory”
phenotype. Central to a strong T cell response is the HLA molecule, and T cell response to
HCMV may be predicted by HLA genotype. An HCMV-activated NK cell can reciprocally
regulate the magnitude of the T-cell response. Using a unique fully autologous in vitro HCMV
infection system, regulatory relationships between NK cells and T cells can be investigated and
identified. Preliminary studies have generated the novel finding that direct interaction of NK cells
with HCMV-infected dendritic cells induces PD-L1 surface expression on NK cells, which
directly inhibits antibody-mediated T cell proliferation. To determine the impact of PDL1+ NK cell
on HCMV antigen specific T cells, T cell responses to HCMV infection will be stimulated by the
use of an artificial antigen-presenting cell pulsed with CMVpp65 peptides. Co-incubation of
CMV-activated PDL1+ NK cells and CMV-sensitized T cells will permit elucidation of regulatory
effects of one lymphocyte on the other. We will utilize a humanized mouse model for the study
of NK and T cell interaction in response to HCMV. The understanding of NK and T cell
relationships developed in the in vitro and in vivo studies will be applied to the study of
expansion and maintenance of adaptive NKG2C+ NK cells in healthy human donors as well as
in patients with CMV reactivation following stem cell transplantation. The availability of blood
samples from a cohort of hematopoietic cell transplant patients with CMV reactivation provides
the unique opportunity to examine the NK and T cell repertoire in the setting of CMV infection.
These studies will describe novel mechanisms that will expand existing knowledge on the
balance of the adaptive and innate immune systems during viral infection and will provide
further insight to mechanisms that can be targeted to prevent reactivation and chronic viral
infection.

## Key facts

- **NIH application ID:** 10268335
- **Project number:** 3P01CA023766-40S1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** KATHARINE C HSU
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $8,562
- **Award type:** 3
- **Project period:** 1997-09-30 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10268335

## Citation

> US National Institutes of Health, RePORTER application 10268335, Project 3: NK and T cell cooperation in CMV infection (3P01CA023766-40S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10268335. Licensed CC0.

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