# Identifying novel regulatory pathways underlying T helper 1 cell immune responses

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $343,812

## Abstract

PROJECT SUMMARY
During the course of an immune response, CD4+ T helper cells identify invading pathogens, proliferate, and 
secrete cytokines to aid in immune-mediated clearance of infection. This results in an initial expansion of
effector CD4+ T cells at the peak of infection. These include effector T helper 1 (TH1) cells, which mediate
immune responses to intracellular pathogens. As pathogen is eliminated, the effector cell population is
reduced, with the exception of a subset of long-lived memory T cells capable of responding more quickly and
robustly to a repeated encounter with the pathogen. This effector-to-memory transition is required for the
generation of both naturally occurring long-term and vaccine-induced immunity.
 In addition to their contribution to the memory cell pool, an emerging body of literature suggests that TH1
cells may also engage in aspects of humoral immunity via plasticity shared with the T follicular helper (TFH) cell
subset. TFH cells engage in cognate interactions with B cells to assist in the production of pathogen-neutralizing
antibodies. Taken together, the above findings suggest that TH1 cells are capable of undergoing stage-specific
phenotypic changes that allow for contributions to humoral and memory cell immunity. Currently, however,
gaps in knowledge exist regarding the molecular mechanisms by which these critical cellular transitions occur.
 Bcl-6 is a transcriptional repressor required for both TFH and central memory T (TCM) cell differentiation.
Recently, we demonstrated that TH1 cells up-regulate Bcl-6-dependent TFH- and TCM-like profiles in response to
diminished antigen stimulation and IL-2 signaling. Intriguingly, these cells also co-express IL-6Rα and IL-7R,
cytokine receptors that support TFH and TCM differentiation, respectively (“IL-6Rα+IL-7R+ cells”). Importantly, our
preliminary data indicate that subsequent exposure to IL-6 or IL-7 differentially regulates TFH and TCM genes in
IL-6Rα+IL-7R+ cells. Therefore, we hypothesize that IL-6- and IL-7-dependent alterations to the transcriptional
landscape of TH1-derived IL-6Rα+IL-7R+ cells allow them to contribute to humoral and memory cell responses.
To test this hypothesis we will 1) determine the IL-6-dependent effects on phenotype and function of IL-6Rα+IL-
7R+ cells, 2) assess the IL-7-dependent effects on phenotype and function of IL-6Rα+IL-7R+ cells, and
3) assess the functional contribution of IL-6Rα+IL-7R+ cells to immune responses in vivo.
 The findings obtained from these studies will be significant, as they will provide novel insight into the
molecular mechanisms that support previously unappreciated roles for TH1 cells in humoral and memory
responses. In doing so, our work will provide the molecular building blocks for the design of novel
immunotherapeutic strategies and increasingly effective vaccines.

## Key facts

- **NIH application ID:** 10377575
- **Project number:** 5R01AI134972-06
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Kenneth Joseph Oestreich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $343,812
- **Award type:** 5
- **Project period:** 2018-05-23 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377575

## Citation

> US National Institutes of Health, RePORTER application 10377575, Identifying novel regulatory pathways underlying T helper 1 cell immune responses (5R01AI134972-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10377575. Licensed CC0.

---

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