Analysis of Neonatal T Cell and Antigen Presenting Cell Functions

Abstract

Neonates are more susceptible to infection than adults and exhibit more intense or prolonged clinical symptoms. The extent to which deficiencies in T cell or antigen presenting cell (APC) function underlie hyporesponsiveness is incompletely understood. Here, immune function of cord 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 IFNγ responses were markedly lower amongst neonates. Reasoning that such stimuli may elicit responses qualitatively different from those that would be obtained following MHC-dependent, cognate T cell activation, alloantigen-specific responses were evaluated. Strikingly, neonates exhibited IFNγ, IL-4 and IL-10 production equal to adults in short term primary 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 using irradiated adult or neonatal cells as stimulators. Finally, the relative capacity of neonatal APC as stimulators of cytokine synthesis 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 IFNγ responses than did adult APC, independent of responder origin. The data argue; (i) T cells are largely immunocompetent at birth, (ii) accessory cell function is not fully mature, and (iii) the widely observed hyporesponsiveness to pathogens may be primarily due to immaturity of APC function or costimulator molecule expression.