Toward Stronger Immunity for Infants
Infants are highly susceptible to infection and respond poorly to vaccination for reasons that are not well understood. Brian D. Rudd, Microbiology and Immunology, and Andrew Grimson, Molecular Biology and Genetics, hypothesize that this vulnerability is due to age-related difference in their cytotoxic killer CD8+ T cells—a type of white blood cell that eliminates cells infected with pathogens. After infection, naive CD8+ T cells differentiate into memory T cells, a form of the cell that can remember pathogens it has already encountered, allowing the host to respond more quickly and robustly. However, in infancy, neonatal T cells are defective at differentiating into these memory cells, enabling re-infection.
Rudd and Grimson’s major goal is to identify the key gene regulatory networks that underlie the differences between neonatal and adult CD8+ T cells, with an eye toward understanding how age-related differences could be exploited to improve infant immunity. MicroRNAs are essential in the function of these cells, and Rudd and Grimson have found discrepancies in the expression of certain microRNAs that are known to alter the behavior of immune cells. Using next-generation sequencing, they are now investigating how particular microRNAs are regulated in both neonatal and adult cells throughout the course of infection. The team is also working with collaborators at the University of Rochester and the Malawi-Liverpool School of Tropical Medicine to determine whether microRNAs can predict vaccine-specific CD8+ T cell responses in newborns. Their innovative approach could lead to new biomarkers for predicting the effectiveness of vaccines and novel therapeutic strategies for enhancing immunity in early life. NIH Award Number: 1U01AI131348-01