ANALYSIS OF NEONATAL T-CELL AND ANTIGEN-PRESENTING CELL FUNCTIONS

Neonates are more susceptible to infection than adults and exhibit mor e intense or prolonged clinical symptoms. The extent to which deficien cies in T cell or antigen presenting cell (APC) function underlie hypo responsiveness is incompletely understood. Here, immune function of co rd blood mononuclear cells (CBMC) from healthy, full-term neonates was compared with adult PBMC. As widely reported, polyclonally-stimulated T cell proliferation was found to be equivalent, while IFN gamma resp onses were markedly lower amongst neonates. Reasoning that such stimul i may elicit responses qualitatively different from those that would b e obtained following MHC-dependent, cognate T cell activation, alloant igen-specific responses were evaluated. Strikingly, neonates exhibited IFN gamma, IL-4 and IL-10 production equal to adults in short term pr imary culture. Both the frequency (Fisher's P < 0.0004) and intensity (<7.5 vs 36.5 pg/ml; Wilcoxon P = 0.005) of alloantigen stimulated IL- 5 responses were elevated among neonates, a finding equally evident us ing irradiated adult or neonatal cells as stimulators ors. Finally, th e relative capacity of neonatal APC as stimulators of cytokine synthes is was assessed by a novel approach using CBMC as both responders and stimulators in MLR. Irradiated neonatal cells consistently stimulated similar proliferative but substantially lower IFN gamma responses than did adult APC, independent of responder origin. The data argue; (i) T cells are largely immunocompetent at birth, (ii) accessory cell funct ion is not fully mature, and (iii) the widely observed hyporesponsiven ess to pathogens may be primarily due to immaturity of APC function or costimulator molecule expression. (C) American Society for Histocompa tibility and Immunogenetics, 1997. Published by Elsevier Science Inc.