# Dissecting the signals that maintain HIV-specific CD8+ T cell exhaustion

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $208,440

## Abstract

Project Summary
This is an application for a K23 award for Dr. Rachel Rutishauser, MD, PhD, a fellow in Infectious Diseases at
the University of California, San Francisco who is establishing herself as a young investigator in patient-
oriented studies of HIV immunology. Her goal is to apply her PhD graduate school background in basic CD8+
T cell biology to study the mechanisms that underlie protective and dysfunctional immune responses in HIV
infection. Nearly forty million people worldwide are infected with HIV and identifying interventions to induce HIV
remission or cure is an NIH high priority research area. Many approaches propose to do so by eliciting
protective HIV-specific CD8+ T cells. However, in order to be effective, these therapies need to overcome HIV-
specific CD8+ T cell exhaustion. Exhaustion is defined as a loss in the regenerative capacity of antigen-
specific CD8+ T cells to proliferate and generate functional effector cells. This K23 award will provide Dr.
Rutishauser with the support to explore how HIV-specific CD8+ T cell exhaustion is regulated by: (1) memory
CD8+ T cell-associated transcriptional programs, (2) tissue microenvironments, and (3) chronic inflammation.
Specifically, she will perform phenotypic, functional, and single-cell transcriptomic analysis of HIV-specific
MHC Class I tetramer+ CD8+ T cells from the peripheral blood, lymph node, and gut tissue of thirty HIV-
infected individuals who she will recruit from the UCSF-based SCOPE cohort from three clinical groups:
individuals who naturally control infection (controllers), as well as non-controllers on and off of antiretroviral
therapy (ART). She will also determine if reducing chronic inflammation can enhance HIV-specific CD8+ T cell
function by leveraging peripheral blood samples from an ongoing NIH-funded clinical study (NCT02272946) of
ART-suppressed HIV-infected individuals who are administered the IL-1β inhibitor, canakinumab. To achieve
these goals, Dr. Rutishauser will be co-mentored by Dr. Peter Hunt, an HIV translational immunologist and
expert in the mechanisms of HIV immune activation, Dr. Joseph Mike McCune, a laboratory-based scientist
who has made several fundamental discoveries about HIV pathogenesis, Dr. Steven Deeks, a leader in the
HIV cure field, and Dr. Mark Ansel, an immunologist with expertise in T cell differentiation. Through a focused
program of mentored training and coursework, the candidate will develop advanced skills in clinical research,
human translational immunology, and single-cell transcriptional analysis. The results of these studies are
anticipated to be directly relevant to HIV cure research and widely applicable to developing treatments for other
disease states in which exhausted antigen-specific CD8+ T cells arise, such as other chronic infections and
cancer. Ultimately, the training and research plans outlined here will support Dr. Rutishauser as she transitions
from being a basic immunologist and clinical infectious dis...

## Key facts

- **NIH application ID:** 10086950
- **Project number:** 5K23AI134327-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Rachel Lena Rutishauser
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $208,440
- **Award type:** 5
- **Project period:** 2018-02-06 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086950

## Citation

> US National Institutes of Health, RePORTER application 10086950, Dissecting the signals that maintain HIV-specific CD8+ T cell exhaustion (5K23AI134327-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10086950. Licensed CC0.

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