# Functional characterization of anergic helper T cells

> **NIH NIH P01** · UNIVERSITY OF MINNESOTA · 2020 · $376,174

## Abstract

Project Summary/Abstract
Autoimmune diseases appear to be caused by dangerous non-tolerant CD4+ T cells specific for an affected
individual's own proteins. Current therapies to control these aberrant T cell responses are unsatisfactory
because they inhibit all T cells, including helpful ones specific for pathogens and cancer cells. The question
now before the field is how to induce self-peptide specific immunological tolerance in CD4+ T cells that cause
autoimmune disease.
Anergy induction in dangerous CD4 T cells and peripheral regulatory T (Treg) cell expansion represent two
potentially important therapeutic strategies to durably control autoimmune disease. Research during the last
grant period established that anergy naturally occurs in the polyclonal CD4 repertoire of healthy mice in
association with the up-regulation of CD73, FR4, and Nrp1. Remarkably, anergic conventional Foxp3– CD44hi
Nrp1+ FR4+ CD73+ CD4 T cells were also observed to differentiate into functional Foxp3+ Treg cells when
adoptively transferred into Treg-deficient Tcra–/– hosts. Therefore, this discovery of `anergy-derived' Treg cells
offers a new avenue for the design of Treg cell therapies to control CD4 T cell-mediated autoimmunity in an
antigen-specific fashion.
Research proposed in this application intends to characterize many of the factors that govern natural anergy
induction and the generation of Treg progenitors, including autoreactive TCRs, tissue-restricted target self-
antigens, tolerogenic signaling events, CpG DNA de-methylations, and anergic gene expression signatures.
Furthermore, proposed experiments will determine how anergy-derived Foxp3+ Treg cells can be generated in
normal hosts and investigate their capacity to suppress autoimmune disease. Finally, experiments will
establish the feasibility of investigating the immunology of anergy and anergy-derived Treg cells in humans.

## Key facts

- **NIH application ID:** 9994827
- **Project number:** 5P01AI035296-26
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Daniel L Mueller
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,174
- **Award type:** 5
- **Project period:** 1997-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994827

## Citation

> US National Institutes of Health, RePORTER application 9994827, Functional characterization of anergic helper T cells (5P01AI035296-26). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9994827. Licensed CC0.

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