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-responsive when compared with adults. The extent to which immaturity of the leucocyte function underlies hyporesponsiveness in the newborn is incompletely understood. In this study flow cytometric techniques were applied to investigate the concurrent expression of a range of surface and intracellular leucocyte functional molecules and cytokines in resting and stimulated cord and adult blood. Production of interleukin (IL)-2 and expression of the components of its receptor, IL-2R alpha/beta/gamma, were investigated. No differences 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 natural killer (NK) cells from newborns expressed IL-2R beta and upregulation of expression was slower. We hypothesize that reduced IL-2R beta may curtail early autocrine IL-2 activation of immune responses in the newborn. This hypothesis was supported by the observation that an increased proportion of stimulated T cells from newborns produced IL-2 at 4 h poststimulation, but at 24 h the proportion was lower than for adult T cells. The very low levels of interferon (IFN)-gamma produced by neonatal T cells and NK cells may also be partly explained by a curtailment of early autocrine activation of T cells. Expression and kinetics of upregulation for other functional molecules 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 secretion 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 mean 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 relation to the inability of newborn infants to mount a febrile response to infection. The findings of lower expression of IL-2R beta and lower production of inflammatory cytokines IL-1 alpha, IL-1 beta and TNF-alpha is a basis for improved understanding of the immunological immaturity of leucocytes in the newborn.
Hodge
S
S
Haematology Department, Women's and Children's Hospital, 72 King William Street, Adelaide, South Australia. sandy.hodge@imvs.sa.gov.au
Hodge
G
G
Flower
R
R
Han
P
P
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D004198:Disease Susceptibility; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007107:Immune System / Q000254:growth & development; D007111:Immunity, Cellular; D007231:Infant, Newborn / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D021122:Protein Subunits; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000378:metabolism
D015703:Antigens, CD; D006684:HLA-DR Antigens; D007376:Interleukin-2; D015850:Interleukin-6; D021122:Protein Subunits; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma