Cord blood leucocyte expression of functionally significant molecules involved in the regulation of cellular immunity

The cellular immune system of the newborn infant is immature and hypo-respo nsive when compared with adults. The extent to which immaturity of the leuc ocyte function underlies hyporesponsiveness in the newborn is incompletely understood. In this study flow cytometric techniques were applied to invest igate the concurrent expression of a range of surface and intracellular leu cocyte functional molecules and cytokines in resting and stimulated cord an d adult blood. Production of interleukin (IL)-2 and expression of the compo nents of its receptor, IL-2R alpha/beta/gamma, were investigated. No differ ences in the proportion of leucocytes producing IL-2R alpha and IL-2R gamma were observed for newborns and adults. A lower proportion of T cells and n atural killer (NK) cells from newborns expressed IL-2R beta and upregulatio n of expression was slower, We hypothesize that reduced IL-2R beta may curt ail early autocrine IL-2 activation of immune responses in the newborn. Thi s hypothesis was supported by the observation that an increased proportion of stimulated T cells from newborns produced IL-2 at 4 h poststimulation. b ut at 24 h the proportion was lower than for adult T cells. The very low le vels of interferon (IFN)-gamma produced by neonatal T cells and NK cells ma y also be partly explained by a curtailment of early autocrine activation o f T cells. Expression and kinetics of upregulation for other functional mol ecules were studied. CD71, HLA-DR, tissue factor and CD152 levels were not significantly different for adults and newborns, suggesting that cord blood leucocytes, in some respects, may demonstrate functional maturity. IL-6 se cretion by stimulated monocytes was also comparable in cord and adult blood . However, IL-1 alpha and IL-1 beta were produced by a lower proportion of monocytes from newborns than adults. Similarly, tumour necrosis factor (TNF )-alpha production for monocytes and T cells was lower in cord blood. The m ean fluorescence intensity for IL-1 alpha, IL-1 beta and TNF-alpha was also lower for leucocytes from cord blood. These findings are significant in re lation to the inability of newborn infants to mount a febrile response to i nfection. The findings of lower expression of IL-2R beta and lower producti on of inflammatory cytokines IL-1 alpha, IL-1 beta and TNF-alpha is a basis for improved understanding of the immunological immaturity of leucocytes i n the newborn.