Identification and characterization of myeloid-derived suppressor cells in neonates

Abstract The neonatal immune system is regarded as immature and consists of impaired T cell and antigen presenting cell function. During pregnancy, suppression of both the maternal and fetal immune responses is necessary to allow successful viviparity. The neonatal immune response may have to overcome this modulated immune environment in the first months of life in order to respond at the level required for protection. It is unclear whether infant immune responses are simply immature or are being actively suppressed. The primary goal of this study was to elucidate mechanisms of infant immune deficiencies, in particular those that are present at birth. We have identified a prevalent population of arginase 1-positive myeloid-derived suppressor cells (MDSC) within neonates (7.7%+/-6.9% of cord blood vs 0.7%+/-0.5% of adult blood mononuclear cells) that may negatively influence infant immune responses. This cell population present at birth has not previously been described in infants, but similar cells have been described to suppress T cell responses in adult cancer patients. In addition, we demonstrate that neonatal MDSC are functional and suppress allogeneic T cell proliferative responses in an arginase 1-dependent manner by an average of 38%. These data suggest that suppressor cell populations, like MDSC, can suppress infant T cell responses. This may be one mechanism behind reduced neonatal immunity resulting in inefficient responses to both infection and vaccination early in life.