Neonates harbour highly active gammadelta T cells with selective impairments in preterm infants

Acknowledgement of the breadth of T-cell pleiotropy has provoked increasing interest in the degree to which functional responsiveness is elicited by environmental cues versus differentiation. This is particularly relevant for young animals requiring rapid responses to acute environmental exposure. In young mice, gammadelta T cells are disproportionately important for immuno-protection. To examine the situation in humans, we compared populations and clones of T cells from term and preterm babies, and adults. By comparison with alphabeta T cells, neonate-derived gammadelta cells show stronger, pleiotropic functional responsiveness, and lack signatory deficits in IFN-gamma production. Emphasising the acquisition of functional competence in utero, IFN-gamma was produced by gammadelta cells sampled from premature births, and, although one month's post-partum environmental exposure invariably increased their TNF-alpha production, it had no consistent effect on IFN-gamma or IL-2. In sum, gammadelta cells seem well positioned at birth to contribute to immuno-protection and immuno-regulation, possibly compensating for selective immaturity in the alphabeta compartment. With regard to the susceptibilities of preterm babies to viral infection, gammadelta cells from preterm neonates were commonly impaired in Toll-like receptor-3 and -7 expression and compared with cells from term babies failed to optimise cytokine production in response to coincident TCR and TLR agonists.