# Development of Localized T Cell Immunity in Pediatric Respiratory Tract Infection

> **NIH NIH K23** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $194,636

## Abstract

7. PROJECT SUMMARY ABSTRACT
Dr. Connors is a Pediatric Critical Care Physician Scientist investigating the generation and establishment of
protective adaptive immune responses in infants and young children, particularly in the context of viral
respiratory tract infections (VRTI). VRTI are ubiquitous in early life and commonly represent the first major
challenge to the developing immune system. The majority of children clear infection without requiring medical
attention, however severe disease from VRTI is the leading cause of respiratory failure necessitating
mechanical ventilation during infancy. Importantly, associations between early life immune responses to
infections and environmental exposures have been made to alterations in pulmonary function in later life. As
immune responses in early life are formative for future protection from pathogens, aberrant responses in early
life can have enduring repercussions. Differentiation of T cells to effector and memory subsets is required for
viral clearance and establishment of protective immunity. Mouse models have demonstrated the importance of
resident memory T cells (Trm) in mediating optimal protection. However neonatal mice T cells demonstrate
transcriptionally distinct responses favoring the generation of terminally differentiated effector T cells over the
establishment of Trm. Studies of human tissue have shown that T cells in tissue are predominately regulatory
(Treg) in nature during infancy with few Trm. Importantly local T cell responses during VRTI are associated
with disease severity in infants and children. The T cell subsets mediating protection during acute infection
and the mechanisms leading to the establishment of long lived memory subsets remains uncharacterized in
early life. Our central hypothesis is that protection from VRTI relies on the local adaptive immune response
and aberrant immune responses during the formative window of infancy are associated with clinical severity.
The aims of this proposal are 1) Determine pathways for T cell differentiation in early life and 2) Define the role
of T cell subsets in VRTI induced Pediatric Acute Respiratory Distress Syndrome (PARDS). This career
development award represents a crucial step in attaining the candidate’s long-term goal of transitioning to an
independent researcher focused on translational studies of adaptive immune responses and critical illness in
children. The academic, mentoring, training, and clinical opportunities afforded by the candidate’s current
environment provide the perfect venues for successful completion of this project and for Dr. Connors to
achieve his goal.

## Key facts

- **NIH application ID:** 9832177
- **Project number:** 5K23AI141686-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Thomas Connors
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $194,636
- **Award type:** 5
- **Project period:** 2018-12-05 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832177

## Citation

> US National Institutes of Health, RePORTER application 9832177, Development of Localized T Cell Immunity in Pediatric Respiratory Tract Infection (5K23AI141686-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9832177. Licensed CC0.

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