# Costimulatory Signals in CD4+ T Cell Activation

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $466,620

## Abstract

Project Summary/Abstract
The two-signal model in which an antigen-presenting cell-derived costimulatory signal, epitomized by CD28, is
needed for T cells to respond maximally to T cell receptor (TCR) stimulation is now part of the immunology
canon and fueled exciting immunotherapies for transplant rejection, autoimmunity, and cancer. Most of the
advances in the costimulation field, however, applied to conventional Foxp3neg CD4+ T cells. Although CD28
enhances the development of Foxp3+ regulatory (Treg) cells as they are selected by high affinity TCR
recognition of self peptides in the thymus, and is required for their autoimmunity-suppressing functions, much
less is known about the costimulatory requirements of Treg cells as they participate in immune responses to
foreign peptides.
During the last funding period, we found that the pre-immune repertoires of CD4+ T cells specific
for foreign peptides from microbes contain both conventional AND Treg cells. Both populations underwent
clonal expansion in the secondary lymphoid organs after infection with a microbe expressing the relevant
peptide but the two populations formed different types of effector cells and generated memory cells with
different efficiencies. Our results lead to the remarkable conclusion that two parallel CD4+ T cell repertoires
exist for each foreign peptide – one composed of conventional naïve cells and a smaller one composed of Treg
cells. Almost nothing is known about the signals that govern the activation of foreign peptide-specific Treg cells
during immune responses to infection or their interactions with conventional T cells responding to the same
peptide. The goal of this project is to determine whether foreign peptide-specific Treg cells require CD28
costimulation during immune responses to infection and if so understand the signal transduction process. We
will also test the intriguing possibility that foreign peptide-specific Treg cells play special roles in regulating the
expansion and differentiation of the conventional T cells specific for the same peptide as both populations
respond during infection. This research could shed light on the understudied role that Treg cells play during
infection and provide new uses for modulation of T cell costimulation.

## Key facts

- **NIH application ID:** 9897522
- **Project number:** 5R01AI027998-31
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Marc Kevin Jenkins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $466,620
- **Award type:** 5
- **Project period:** 1989-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897522

## Citation

> US National Institutes of Health, RePORTER application 9897522, Costimulatory Signals in CD4+ T Cell Activation (5R01AI027998-31). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897522. Licensed CC0.

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