# Innate Recognition of Allogeneic Non-Self

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $413,762

## Abstract

Abstract
Despite significant reduction in acute rejection rates, long-term allograft survival remains
stagnant, hovering at around a half-life of 10 years for most transplanted organs. A principal
cause of poor long-term graft outcomes is persistent host immune activation leading to chronic
rejection. We propose here that persistent immune activation is driven by the innate immune
system, specifically by monocytes which recognize allogeneic non-self and acquire memory to
it. Monocytes sense non-MHC and MHC polymorphisms on allogeneic tissues and acquire the
ability to mount an enhanced recall response specific to donor MHC. This response results in
sustained graft infiltration by mature, IL-12+, monocyte-derived DCs that maintain an
inflammatory Th1 response and are critical for allograft rejection. The goal of this grant
application is to investigate in Aim 1 the molecular and cellular mechanisms of monocyte
memory generation and specificity to allogeneic MHC, and to determine in Aim 2 the
contribution of monocyte memory to chronic allograft rejection. Completion of the proposed
studies is likely to have a significant impact on organ transplantation by uncovering novel innate
immune system targets to prevent or treat rejection.

## Key facts

- **NIH application ID:** 9942365
- **Project number:** 5R01AI099465-08
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Fadi G. Lakkis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $413,762
- **Award type:** 5
- **Project period:** 2012-09-27 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942365

## Citation

> US National Institutes of Health, RePORTER application 9942365, Innate Recognition of Allogeneic Non-Self (5R01AI099465-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9942365. Licensed CC0.

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