# Tertiary Lymphoid Organs in Transplantation

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $385,600

## Abstract

Abstract
In solid organ transplantation, immunosuppressive therapy has significantly improved short-term organ allograft
survival by reducing acute rejection rates. However, chronic rejection - mediated by T cells, antibodies (Abs), or
both - has not declined in incidence and remains an important obstacle to long-term allograft survival. A likely,
important contributor to the pathogenesis of chronic rejection is the formation of tertiary lymphoid organs (TLO)
within the graft. Evidence that TLO play a causative role in rejection derives from both mice and humans, as TLO
have been documented in a majority of chronically rejected mouse and human allografts, and experimental
models have shown that they support naïve T and B cell activation and influence graft outcome. Moreover,
analysis of human renal allograft biopsies has demonstrated B cell hypermutation and Ab production within TLO.
Together, these studies support the hypothesis that TLO are niduses of local (intragraft) immune activation in
chronic allograft rejection. In Aim 1 of this grant application, we will establish the cause-effect relationship
between TLO and chronic renal transplant rejection in the mouse. In Aim 2, we will investigate the cellular and
cytokine mechanisms responsible for TLO formation in allografts, with particular emphasis on innate lymphoid
cell (ILC) subsets. In Aim 3, we will delineate the specific immunologic functions of TLO in chronic rejection, with
focus on B cell activation and antibody production. The proposed studies address the unmet challenge of treating
and preventing chronic rejection and will also shed light on other conditions in which TLO play a prominent role,
such as autoimmunity and cancer.

## Key facts

- **NIH application ID:** 10136512
- **Project number:** 5R01AI145881-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Martin H Oberbarnscheidt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,600
- **Award type:** 5
- **Project period:** 2019-05-17 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136512

## Citation

> US National Institutes of Health, RePORTER application 10136512, Tertiary Lymphoid Organs in Transplantation (5R01AI145881-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10136512. Licensed CC0.

---

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