# Pregnancy-induced T cell exhaustion: an opportunity to reduce immunosuppression

> **NIH NIH K08** · UNIVERSITY OF PENNSYLVANIA · 2020 · $196,236

## Abstract

PROJECT SUMMARY (ABSTRACT)
Pregnancy is a common alloimmunizing event that impacts transplant access and outcomes among women.
Although T cells of the maternal immune system are routinely activated by fetal alloantigen, it is unclear
whether T cells stimulated by fetal antigen differentiate into canonical memory cells during pregnancy. The
long-term fate and recall potential of these antigen-experienced T cells in the maternal repertoire are of
particular importance to female transplant recipients, whose T cells may be capable of rapid rejection of a
donor organ that shares tissue antigens with a prior pregnancy. Unfortunately, our poor understanding of T cell
fate in women with a history of pregnancy has contributed to significant gender disparity in transplantation.
Preliminary data in our mouse model suggest that fetal antigen during pregnancy promotes the differentiation
of CD8+ T cells that persist in the maternal repertoire but have restricted functionality. While these T cells can
still mediate rapid allograft rejection, they appear to be distinct from memory T cells that differentiate during
other types of alloimmunization. Different populations of antigen-experienced T cells in alloimmunized
transplant recipients may have unique requirements for immunosuppression. In this proposal, we will
investigate how populations of antigen-experienced T cells induced by either pregnancy or transplantation
differ from one another (Aim 1) and determine whether these differences promote immunosuppression
reduction strategies in women (Aim 2). We anticipate that the knowledge generated by these studies will alter
current immunosuppression strategies to improve the care of alloimmunized transplant recipients.

## Key facts

- **NIH application ID:** 9934104
- **Project number:** 5K08AI130365-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** PAIGE M PORRETT
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,236
- **Award type:** 5
- **Project period:** 2018-06-01 → 2020-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934104

## Citation

> US National Institutes of Health, RePORTER application 9934104, Pregnancy-induced T cell exhaustion: an opportunity to reduce immunosuppression (5K08AI130365-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934104. Licensed CC0.

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