Antenatal glucocorticoid administration for pulmonary immaturity modulates regulatory T cell subset distribution in cord blood

A number of studies in laboratory rodents have shown how glucocorticoid hormones (GC) alter thymus functionality. Conversely, how GC influence normal human thymus functionality is largely unknown for obvious ethical reasons. Current guidelines state that healthy pregnant women destined to preterm delivery should be considered for antenatal GC (AGC) administration before delivery to facilitate fetal lung maturation. We reasoned that this procedure exposes fetal thymus to GC and investigated AGC impact on fetal thymus functionality in 15 pregnant women (8 on GC and 7 untreated) by measuring changes occurring in major T cell subset and recent thymic emigrant frequency in newborn’s cord blood. Fetal thymus morphology was assessed sonographycally. Despite AGC reduced thymic transverse diameter and perimeter (p< 0.05 both parameters), no measurable change occurred in recent thymic emigrant frequency and major T cell subset, including regulatory T cell (CD25+Foxp3+CD4+T cells, T-regs). Conversely, AGC reduced the proportion of CD45RA+ T-regs (78.4 ± 7.15% and 67.8 ± 5.45%, mean ± SD, untreated and treated subjects, respectively, p<0.02) and this effect was selective for T-regs, as CD45RA expression in conventional CD4+ T cells was not modified by AGC (92.9 ± 3.5 % and 94.4 ± 2.4 %, mean ± SD, untreated and treated subjects, respectively. However, CD45RA modulation did not affect Treg functionality. The accumulation of T-regs with a CD45RA− phenotype induced by AGC may reflect a reduced T-reg output from thymus followed by homeostatic expansion in the periphery for T-reg pool replenishment, as in adults, or a thymic export of not yet mature T-regs that maintain their CD45RA− intrathymic phenotype. Correspondence to: Andrea Fattorossi, Laboratory of Immunology, Polo della Donna e del Bambino, Fondazione Policlinico Gemelli, L.go A. Gemelli 8, 00168, Roma, Italy, Tel: ++390630158262; Fax: ++39063051160; E-mail: [email protected]