# Self-renewing Lymphocyte Division in The Immune Response

> **NIH NIH R56** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $401,867

## Abstract

Project Summary/Abstract
When a T lymphocyte is engaged in an immune response, it must divide and produce
functional daughter cells, often repeatedly. To maintain continued, clonal production of
fresh effector T cells requires that some daughter cells self-renew instead of
differentiating. Our laboratory identified the activating signals that induce progenitor T
cells to undergo irreversible commitment to differentiation. Preservation of self-renewal,
however, requires a dampening mechanism to oppose full activation. Among the most
critical signals that dampen T cell activation are the inhibitory receptors, which are now
key targets of a revolutionary approach to unleash T cell attack against tumors. While
blockade of inhibitory receptors offers clinical benefit in some cases, many treated
patients do not experience durable anti-tumor immunity. This project addresses a novel
and clinically important question that may represent a major barrier for improving the
efficacy of inhibitory receptor blockade: Are inhibitory signals an essential part of a
regenerative mechanism allowing some T cells to self-renew as their kindred cells
undergo differentiation? Using preclinical models of cancer and chronic-active infectious
diseases, 3 specific aims will be addressed: (1) Determine if inhibitory receptor
blockade impacts the balance of T cell differentiation and self-renewal in vivo, (2) Define
the cell biological mechanisms that support T cell self-renewal under in vivo conditions
of repetitive, high-level antigen activation and response intensification by inhibitory
blockade, and (3) Test whether the efficacy of inhibitory receptor blockade will be
improved by addition of agents that promote T cell self-renewal. The results of these
studies could offer novel immune response biomarkers, new strategies for vaccination,
and novel or repurposed compounds to augment the efficacy of immunotherapy.

## Key facts

- **NIH application ID:** 10395010
- **Project number:** 2R56AI076458-11
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** STEVEN L REINER
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $401,867
- **Award type:** 2
- **Project period:** 2008-02-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395010

## Citation

> US National Institutes of Health, RePORTER application 10395010, Self-renewing Lymphocyte Division in The Immune Response (2R56AI076458-11). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10395010. Licensed CC0.

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