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Contributions of neonatal-origin CD4 T cells to immunity and tissue function

Award Number: R01AI201177
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/03/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

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Contributions of neonatal-origin CD4 T cells to immunity and tissue function - Project Summary Neonatal T cells have distinct properties that represent an adaption to the rapidly changing tissue environment during early life. Those features include a T cell receptor (TCR) repertoire skewed towards self-reactivity, enhanced effector function, rapid proliferation, and efficient tissue seeding. Importantly, T cells of neonatal origin persist into adulthood and represent a functional layer of the adult immune system. Most of the work has centered on neonatal-derived CD8 T cells and their contributions to early pathogen clearance. We have developed a novel timestamping system that allows us to track T cells of neonatal origin and their persistence and functional contributions to adult immunity. We will leverage this system to uncover fundamental features of the neonatal layer of CD4 T cells and their contribution to immunity throughout the lifespan of an animal. Our initial characterization confirmed that neonatal-origin CD4 T cells persist into adulthood and likely contribute to functional immunity by occupying a specialized niche. Intriguingly, neonatal-origin CD4 T cells were enriched for memory-phenotype cells, a cell state usually associated with rapid effector capacity and innate (TCR-independent) response capacity but incompletely understood. Do neonatal-origin CD4 T cells contribute to early innate-like responses during acute infections? What are the underlying regulatory networks that facilitate memory-phenotype responses? We hypothesize that neonatal-origin CD4 T cells represent an important functional layer of the adult immune system as rapid responders to acute infection through their persistence as memory-phenotype cells. Using our timestamping models, we will leverage access to the neonatal CD4 T cell layer in adult mice to define their functional contributions to address the following questions: 1) What is the breadth of innate responsiveness of these neonatal-origin memory-phenotype cells, and can we define the underlying transcriptional network? 2) Do memory-phenotype cells help protect the host during early infection? 3) Can neonatal-origin T cells retain their effector properties in settings of chronic antigen exposure? Are they better anti-tumor effectors? 4) Can we leverage the enrichment of neonatal-origin Treg cells in adipose and skin to uncover the organizing principles of how they promote tissue homeostasis? Our work will provide foundational insights into the contributions of the neonatal CD4 T cell layer to the robustness of the adult immune system through their rapid elaboration of effector programs linked to their memory-phenotype features. Elucidation of the programs governing rapid effector responses for neonatal-origin CD4 T cells and neonatal-origin Treg-mediated tissue homeostasis will pave the way towards therapeutic targeting or manipulation to enhance effector responses and promote tissue robustness.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $533,926 )
2026	2026	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	1	9/3/2026	NEW	$533,926
														Subtotal = $533,926

Grand Total All Awards = $533,926

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Contributions of neonatal-origin CD4 T cells to immunity and tissue function

Award Number: R01AI201177

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/03/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

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