# Antibody Mediated Rejection and Post-transplantation Anti-Viral Immunity in Aging

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $636,774

## Abstract

The proportion of aged patients undergoing solid organ transplantation is steadily increasing. Despite this,
therapeutics to treat rejection are designed based on a youthful immune system. The aged immune system
likely has unique mechanisms controlling transplant rejection which increase susceptibility to opportunistic
infections. T follicular helper (Tfh) cells play a critical role in mediating B cell responses, including antibody
mediated rejection (AbMR). Newer data suggest Tfh cells are a heterogeneous composition of uniquely
functioning cell subsets. Therefore, it may be possible to uncouple transplant rejection from anti-viral immunity.
However, a fundamental understanding of Tfh differentiation stages and how these function to promote
alloimmunity and rejection in the context of aging is lacking. The objective of the proposed studies is to elucidate
how the aged immune system controls alloimmunity in the context of kidney and heart transplantation. We
hypothesize that the inflamm-aging environment causes Tfh rewiring which promotes B cell alloimmunity. We
also hypothesize that targeting specific Tfh stages may uncouple allo- and anti-viral immunity. To test these
hypotheses, we will: 1) determine how aging alters Tfh-mediated B cell alloimmunity after solid organ
transplantation, 2) assess how the inflamm-aging environment causes Tfh rewiring to induce a senescence-like
state, and 3) determine if nanoparticle therapy to age-associated Tfh rewiring can alleviate transplant immunity
while maintaining anti-viral immunity. We will pursue these aims using innovative strategies to identify and
perturb Tfh cell stages in vivo during kidney transplantation in aged mice. We will combine these innovative
tools with transcriptomics, metabolomics and high-dimensional analyses of B cell responses at the single cell
level. The expected outcome of these studies is to determine mechanisms controlling allo- and anti-viral
immunity in aging. These studies are significant because they will provide strategies to prevent rejection in
aging while limiting susceptibility to infection.

## Key facts

- **NIH application ID:** 10862426
- **Project number:** 1P01AI175397-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Peter The Sage
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $636,774
- **Award type:** 1
- **Project period:** 2024-05-03 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862426

## Citation

> US National Institutes of Health, RePORTER application 10862426, Antibody Mediated Rejection and Post-transplantation Anti-Viral Immunity in Aging (1P01AI175397-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10862426. Licensed CC0.

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