# Role of Gestational Age in T-Cell Receptor (TCR) Repertoire Development and Response to Infant Respiratory Viral Infection

> **NIH NIH R03** · DREXEL UNIVERSITY · 2020 · $78,250

## Abstract

Project Summary/Abstract
Despite a reduction in death rates attributed to respiratory distress syndrome and bronchopulmonary dysplasia
in extremely premature infants over the past 20 years, death caused by infection has remained the same or has
increased in rate. Specifically, respiratory viral infections contribute substantially to global fetal and infant losses
and disproportionately affect preterm neonates. Of all deaths secondary to a respiratory viral infection, 55%
occur in a neonate born before 30 weeks gestation. Over the past three years of a Career Development Award
(K08) from the NIAID, Dr. Carey has developed the laboratory and leadership skills necessary for this application.
Given the susceptibility of preterm infants to respiratory viruses, and the importance of CD8+ T cells in combating
these pathogens, T-cell receptor (TCR) repertoire analysis was performed of naïve CD8+ T cells in viable, live-
born extremely preterm neonates (23-27 weeks gestation) and compared them to term neonates (37-41 weeks
gestation), young children (16 months to 56 months) and adults (25 to 50 years old). Analysis revealed that
preterm neonates have a repertoire characterized by shorter CDR3β regions, with a striking number of germline
public clonotypes which exhibit convergent recombination. This degree of sharing indicates that there is a
common, developmentally-determined “beginner” repertoire, which is shaped by germline sequences. Therefore,
we hypothesize that preterm infants are susceptible to infection because their naïve T cell repertoire is
dominated by germline, public TCR clones. This developmentally-determined beginner repertoire could
provide a broad-based, cross-reactive protection, but not with the specificity and potency of an older child. Based
on our preliminary work with a neonatal murine model of influenza infection and our comprehensive human naïve
CD8+ TCR repertoire analysis from the edges of viability to adulthood, we propose the following specific aims.
First, perform naïve CD4+ T cell repertoire analysis in neonates, infants and adults. Second, determine the TCR
repertoire of infants infected with a respiratory virus. For this pilot study, we seek to enroll 30 infants in the two-
year study period, with roughly 15 former preterm neonates and 15 former term neonates. CD8+ T cells and
regulatory CD4+ T cells will be isolated and repertoire analysis performed. Little is known about the CD8+ T cell
and Treg response during acute infection in the first year of life. Together, the results from this R03 pilot project
will provide valuable information about the development of the complete naïve T cell repertoire, how differences
in the naïve T cell repertoire might impact the response to a respiratory viral infection, and the role of Tregs in
preterm versus term infants during infection. The results from this R03 study will provide key data to support a
subsequent R01 submission. In this future R01 proposal, there will be an expanded d...

## Key facts

- **NIH application ID:** 9822151
- **Project number:** 5R03AI139727-02
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Alison J Carey
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $78,250
- **Award type:** 5
- **Project period:** 2018-11-13 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9822151

## Citation

> US National Institutes of Health, RePORTER application 9822151, Role of Gestational Age in T-Cell Receptor (TCR) Repertoire Development and Response to Infant Respiratory Viral Infection (5R03AI139727-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9822151. Licensed CC0.

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