# A novel population of PLZF+CD8+ regulatory T cells: phenotype and function

> **NIH NIH R56** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $557,738

## Abstract

Immune tolerance mediated by regulatory T cells (Treg) is important in the control of inflammatory and
autoimmune diseases. The detailed biology of CD8 Treg is lacking due to the absence of molecular markers to
distinguish them from conventional CD8+ T cells (CD8conv), as Foxp3 expression is for CD4 Treg. We have
discovered that the expression of the promyelocytic leukemia zinc finger (PLZF) transcription factor together with
other markers distinguishes a novel, unconventional CD8 Treg population from other CD8conv as well as
unconventional T cells. Though, CD8 Treg are enriched in liver of naïve mice, they are also present in other
lymphoid tissues and in human PBMC and display an activated/memory phenotype and attributes of innate-like
T cells. Our long-term goal is to characterize the biology of CD8 Treg in both mice and humans and to understand
the negative feedback regulatory mechanism(s) employed by CD8 Treg that limits excessive immune stimulation.
These studies are highly significant as they will have potential to not only uncover a key CD8 Treg-mediated
molecular mechanism(s) involved in immune homeostasis, but also will have major implications for the
development of new immune therapies in autoimmune diseases. The objective of this grant is to characterize
the transcriptome signature, development, activation/expansion and mechanism of regulation of CD8 Treg in
murine models and also to determine their molecular and suppressive functions in humans. The central
hypothesis is that the PLZF transcription program allows acquisition of innate-like and memory features in CD8
Treg that enables them to control promptly and effectively inflammatory autoimmune responses by targeting
activated T cells as well as APCs. Based upon our critical preliminary data that indicate a unique phenotype of
CD8 Treg (PLZF+TCRαβ+CD8αα+), we propose the following specific aims: Aim 1. To determine their unique
transcriptional program and molecular pathways, single cell RNA sequencing analysis of CD8 Treg subsets will
be carried out in both the periphery and in the inflamed CNS. A bone marrow chimeric approach will be used to
determine the role of PLZF transcription factor in their development and function; Aim 2. To determine the critical
role of the cross-presentation mechanism in the physiological induction of CD8 Treg, mice genetically lacking
cDC1 will be used. Genetic depletion of CD8 Treg in PLZFF/F mice will decipher their role in the recovery and
resistance from experimental autoimmune encephalomyelitis. A critical role for the regulatory molecules,
including CD200 and Fgl2, in the inhibition of DC function and/or Th1/Th17 induction will be elucidated; and Aim
3. To characterize the transcriptional signature and suppressive mechanism(s) involved in human CD8 Treg,
sorted cells from peripheral blood of healthy individuals will be used. Collectively, our proposed studies will have
a major impact in the emerging field of unconventional T cells and in the CD8 ...

## Key facts

- **NIH application ID:** 10247312
- **Project number:** 1R56AI146071-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Vipin Kumar
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $557,738
- **Award type:** 1
- **Project period:** 2020-09-17 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247312

## Citation

> US National Institutes of Health, RePORTER application 10247312, A novel population of PLZF+CD8+ regulatory T cells: phenotype and function (1R56AI146071-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10247312. Licensed CC0.

---

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