Fellow Physician University of Iowa Hospitals and Clinics Iowa City, IA, United States
Background: Extremely premature infants have altered immune responses, which makes them more susceptible to infection. These altered responses are not well characterized or understood.
Objectives: Determine how T cell subset proliferation differs between extremely premature infants, late preterm infants, term infants and adults.
Design/Methods: Residual blood samples from extremely preterm infants (22-26 weeks’ gestation) and cord blood samples from late preterm (>33 weeks’ gestation) and term infants (>37 weeks’ gestation) were collected. Adult blood samples were collected from healthy volunteers. CD4+ T cells were isolated and stimulated with 50 ng/mL IL-2 and/or anti-CD3/anti-CD28 beads for 72 hours. Following stimulation, flow cytometry was used to evaluate surface CD3, CD4, CD8 and CD25 expression and intracellular Foxp3 expression. Controls included a subset of cells prior to stimulation and unstimulated cells following 72 hours of culture.
Results: Prior to stimulation, extremely preterm T cells were significantly more likely to be CD3+ only while the other age groups had larger CD4+ populations. Following stimulation with IL-2 and anti-CD3/28 beads, there was a significant increase in CD25+/Foxp3+ cells in the extremely preterm cohort compared to all other age groups.
Conclusion: T cells from extremely preterm infants were more likely to proliferate as CD25+/Foxp3+ regulatory T cells following stimulation, while other age groups were more likely to proliferate as CD4+ T helper cells. This suggests that extremely preterm infants tend towards an anti-inflammatory, regulatory adaptive immunity motif, which likely contributes to their increased risk of infection. We are working to further characterize genetic changes that drive these differential responses.
