Advancing the health and well-being of animals and people


Principal Investigator: Brian Rudd

Contact Information: Email: bdr54@cornell.edu; Phone: 607-253-4418
Sponsor: NIH
Grant Number: 4R00HD067290-2
Title: Neonatal Infections and Memory T Cell Repertoire
Annual Direct Cost: $168,687
Project Period: 09/22/2011-08/31/2014

DESCRIPTION (provided by applicant): Neonates are particularly susceptible to chronic persistent infections. The goal of this proposal is to link various stages of development with diversification of the CD8+ TCR repertoire and immune defense. To accomplish this goal, we will investigate the capacity of antigen-specific neonatal and adult CD8+ T cells to generate appropriate immune responses against persistent infections (e.g HSV-1 and CMV). Our overall focus is on determining the long-term consequences of persistent infections in neonates by examining to what extent neonatal CD8+ T cell clonotypes are maintained through development and provide immune defense as adults. Our central hypothesis is that infections early in life 'lock-in' a less diverse and structurally distinct CD8+ TCR repertoire that hinders immune surveillance during adulthood. We predict that persistent neonatal infections alter the clonal composition of tissue resident memory cells and their ability to control latency later in life. This will be tested by examining the ability of HSV-1 to sequester the neonatal repertoire into the trigeminal ganglia and correlate repertoire diversity with immune surveillance and functionality during latent infection. Knowledge gained from these studies will better inform us on how infections early in life alter the clonal composition of the adult memory T cell pool and provide insight into improving long-lasting T cell immunity during critical stages of early development.