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

International Journal of Molecular Sciences

Simon C. Barry¹  Michael J. Stark¹  Alex Quach²  Khalida Perveen²  Antonio Ferrante²  Charles S. Hii²  Susan L. Prescott³ 

[1] Adelaide School of Medicine and the Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia;Department of Immunopathology, SA Pathology at the Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia;School of Paediatrics and Child Health, University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia;

关键词: neonate;    cord blood T cells;    CD4⁺ and CD8⁺ T cells;    T cell maturation;    Th1 and Th2/9 subsets;    PKC isozymes;   

DOI  :  10.3390/ijms222312650

来源: DOAJ

【 摘 要 】

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 PKCζ correlating with increased risk of developing allergy and associated decrease in interferon-gamma (IFN-γ) producing T cells. Interestingly, these lower levels of PKCζ 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 PKCζ relates to other PKC isozymes and whether their levels influence maturation into IFN-γ producing T cells. There is also no information on PKCζ 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, PKCζ, β2, δ, μ, ε, θ and λ/ι 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 PKCζ, β2 and μ, and 1–2 days for PKCδ, ε, θ and λ/ι. Only CBTC PKCζ isozyme levels correlated with cytokine production, with a positive correlation with IFN-γ, 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 PKCζ levels as a biomarker for risk of allergy development and identify a period in which this can be potentially ‘corrected’ after birth.

【 授权许可】

Unknown