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409 T-CELL REGULATION IN NEONATES MAY MODIFY IMMUNE RESPONSE TO INTRACELLULAR PATHOGENS.
  1. M. E. Awoniyi1,
  2. S. S. Sing1,
  3. C. W. Wilson1
  1. 1Department of Immunology, University of Washington, Seattle, WA

Abstract

A delicate balance in host immunity is constantly maintained, allowing for potent responses during infection and quickly silencing these responses once infection resolves. Perturbations in this balance result in increased susceptibility to infection, immune cell-mediated injury to the host, or both. Part of the answer of better stabilizing our immune defense is the advent of vaccines. Although currently available vaccines for neonates use are able to elicit robust antibody responses, this type of response provides immunity for some infections; it does not provide immunity to pathogens, such as Listeria monocytogenes (Lm), that primarily reside in the intracellular compartment, which require antigen, specific Th1, and CD8 T cells. Lm is a major pathogen in the neonate and in other immune-compromised hosts, causing gastroenteritis, abortion, sepsis, and CNS infections. A recent discovery that could provide some answers could be a fraction of CD4 T cells, called T-regulatory cells (or simply Tregs), which have recently been identified to play an active regulatory role by suppressing the function of other CD4 and CD8 T cells. Neonatal cells do not respond well to some vaccines due to their natural bias toward a Th2 response; given the potential reactivity of fetal T cells, it seems reasonable to hypothesize that neonatal Tregs cells contribute to apparent fetal unresponsiveness by dominant tolerance mechanisms, perhaps to prevent destructive reactivity to maternal antigens. Preliminary data to ascertain this hypothesis indicated that neonatal murine Tregs transcriptionally expressed more of the foxp3 gene compared with adults Tregs per cell basis, and these data could lend themselves to function. Comparing the transfer of donor adult versus neonatal Tregs within the responder Lm-infected mice, we hope to test the ability of neonatal versus adult Tregs to suppress the action of same responder population (adult splenocytes) by measuring their ability to produce a Th1 cytokine (IFN-γ). Unfortunately, adult Tregs resulted in greater suppressive activity than their neonatal counterpart did.

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