Heterogeneity in the CD4 T cell compartment and the variability of neonatal immune responsiveness

Over the past decade, it has become clear that T cell immune responses in both murine and human neonates are very heterogeneous, running the gamut from poor or deviant responsiveness to mature, adult-like inflammatory function. How this variability arises is not well understood but there is now a great deal of information suggesting that differences in the T cell compartments in neonates vs adults play important roles. A number of cell types or processes are qualitatively or quantitatively different in the neonate. These include (a) alternate epigenetic programs at the Th2 cytokine locus, (b) enhanced homeostatic proliferation, (c) a relative abundance of fetal-origin cells, (d) a greater representation of recent thymic emigrants, (e) high proportions of potentially self-reactive cells, (f) a developmental delay in the production of regulatory T cells, and (g) cells bearing TCR with limited N region diversity. Different conditions of antigen exposure may lead to different environmental signals that promote the selective responsiveness of one or more of these populations. Therefore, the variability of neonatal responses may be a function of the heterogeneous nature of the responding T cell population. In this review, we will describe these various subpopulations in detail and speculate as to the manner in which they could contribute to the heterogeneity of neonatal immune responses.