Project 454641

The immune cells of newborns and adults differ in their ability to combat infectious diseases. This renders newborns susceptible to certain diseases that are not a concern to adults with fully developed immune systems. One of the reasons for this immune suppression is to prevent a harmful autoimmune response where the newborn's own immune cells attack other cells within the body. This is important in fetal development and immediately after birth when the newborn may be exposed to a variety of helpful bacteria. To prevent this autoimmune response, newborns produce a large number of immune cells called regulatory T cells that limit the immune response to their own cells. These regulatory T cells are generated from a precursor cell type called naive CD4 T cells, which have not differentiated into one of many other possible T cell lineages. The purpose of this project is to determine whether the naive CD4 T cells in newborns have a metabolism that differs from that of adults. We hypothesize that it is these differences in metabolism which contribute to the unique response of newborns to disease. Our early data shows that the naive CD4 T cells in newborns do have metabolic differences when compared to naive CD4 T cells in adults. One key pathway that may differ between the two is cellular respiration, where the mitochondria within cells generate a large amount of energy in the presence of oxygen. It is possible that newborns have less active mitochondria in their naive CD4 T cells than adults, and this could contribute to their tendency to develop into regulatory T cells. If metabolism contributes to the function of newborn immune cells, then perhaps metabolism could be regulated to prevent severe disease.