Characterization of the Transient Deficiency of PKC Isozyme Levels in Immature Cord Blood T Cells and Its Connection to Anti-Allergic Cytokine Profiles of the Matured Cells

Cord blood T cells (CBTC) from a proportion of newborns express low/deficient levels of some protein kinase C (PKC) isozymes, with low levels of PKC zeta correlating with increased risk of developing allergy and associated decrease in interferon-gamma (IFN-gamma) producing T cells. Interestingly, these lower levels of PKC zeta were increased/normalized by supplementing women during pregnancy with n-3 polyunsaturated fatty acids. However, at present, we have little understanding of the transient nature of the deficiency in the neonate and how PKC zeta relates to other PKC isozymes and whether their levels influence maturation into IFN-gamma producing T cells. There is also no information on PKC zeta isozyme levels in the T cell subpopulations, CD4(+) and CD8(+) cells. These issues were addressed in the present study using a classical culture model of neonatal T cell maturation, initiated with phytohaemagglutinin (PHA) and recombinant human interleukin-2 (rhIL-2). Of the isozymes evaluated, PKC zeta, beta 2, delta, mu, epsilon, theta and lambda/iota were low in CBTCs. The PKC isozyme deficiencies were also found in the CD4(+) and CD8(+) T cell subset levels of the PKC isozymes correlated between the two subpopulations. Examination of changes in the PKC isozymes in these deficient cells following addition of maturation signals showed a significant increase in expression within the first few hours for PKC zeta, beta 2 and mu, and 1-2 days for PKC delta, epsilon, theta and lambda/iota. Only CBTC PKC zeta isozyme levels correlated with cytokine production, with a positive correlation with IFN-gamma, interleukin (IL)-2 and tumour necrosis factor-alpha (TNF), and a negative association with IL-9 and IL-10. The findings reinforce the specificity in using CBTC PKC zeta levels as a biomarker for risk of allergy development and identify a period in which this can be potentially 'corrected' after birth.