# Evolution and Durability of Human T and B Cell Responses

> **NIH NIH U19** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $3,474,901

## Abstract

Human memory B and T cells (Bmem, Tmem) can be found in circulation and residing in lymphoid and non-
lymphoid tissues. After infection and vaccination, we can follow antigen (Ag)-specific phenotypically-defined
memory cells in blood, but we can't easily track Ag-specific clones of memory cells in blood over time and the
cells are lost to us if they leave circulation and move into tissues. Our knowledge of the antigen (Ag)-specific
Tmem and Bmem compartments in tissues, particularly non-lymphoid tissues, has been largely limited to single
timepoint analyses. While we have learned much about the human immune system from these static and serial
approaches, at the end of the day, these analyses still only provide us with “immune snapshots” of the Ag-specific
memory clones and tissue resident memory cells. This limits us from asking key questions such as which signals
facilitate or prevent the recruitment, retention, and survival of specific populations of tissue resident human
memory cells. We are also unable to precisely measure the evolution of Ag-specific clones over time or assess
whether microenvironment or immune perturbations influences the evolution and durability of these clones of
cells. This knowledge gap is the basis for the Cooperative Centers in Human Immunology (CCHI) U19 application
entitled “Evolution and Durability of Human T and B cell Responses”. The goal of this Program is to address the
knowledge gap by leveraging our access to samples from organ transplant recipients to: (i) monitor cellular
trafficking of memory cells from circulation into tissues over time; (ii) study the evolution of memory cells that
reside in the tissue or respond to tissue specific Ags; and (iii) assess the durability of these memory populations
over time and in response to changes in the environment. The central hypothesis addressed in this program is
that the human immune memory compartment is constantly evolving in response to local and systemic signals
that influence both the durability and reactivity profile of these cells. We will address this hypothesis in three
research Projects that are supported by three scientific service Cores. Project 1 will address the factors that
control the evolution and durability of memory B cells and antibody secreting cells that contribute to organ failure
and rejection in kidney transplant patients. Project 2 will study the generation and durability of memory T cells
that reside in the endometrium of uterus transplant patients. Project 3 will assess B cell and antibody responses
in lung transplants. The three science service Cores will support the overarching goals of the Program and will
provide the individual projects with the tools needed to track and analyze memory T cells, memory B cells and
antibodies. We believe that the studies in this Proposal are important because they are designed to address
fundamental questions about the generation, evolution and durability of human memory B and T cells. In the
future, ...

## Key facts

- **NIH application ID:** 10824851
- **Project number:** 1U19AI181105-01
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Frances E. Lund
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,474,901
- **Award type:** 1
- **Project period:** 2024-04-16 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824851

## Citation

> US National Institutes of Health, RePORTER application 10824851, Evolution and Durability of Human T and B Cell Responses (1U19AI181105-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10824851. Licensed CC0.

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