ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Transient deficiency of PKC isozymes in immature cord blood T cells and their development into Th1/Th2 cell bias (#256)

Khalida Perveen 1 2 3 , Alex Quach 1 2 , Michael J Stark 2 4 , Susan L Prescott 5 6 , Simon C Barry 2 , Charles S Hii 1 2 , Antonio Ferrante 1 2 7
  1. Department of Immunopathology, SA Pathology at the Women’s and Children’s Hospital, North Adelaide, SA, Australia
  2. Adelaide School of Medicine and the Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia
  3. Department of Immunopathology, SA Pathology at the Women and Children Hospital, North Adelaide 5006, SA, Australia
  4. Department of Neonatal Medicine, Women’s and Children’s Hospital, North Adelaide, SA, Australia
  5. School of Paediatrics and Child Health, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009,, Australia
  6. The ORIGINS Project, Telethon Kids Institute, Perth Children’s Hospital,15 Hospital Avenue, Nedlands, WA 6009, Australia
  7. School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia

Cord Blood T cells (CBTC) express low levels of some protein kinase C (PKC) isozymes, with low levels of PKCζ correlating with increased risk of developing allergy and T cells with a Th2 cytokine bias. Interestingly, lower levels can be normalized by supplementing women during pregnancy with n-3 polyunsaturated fatty acids. Once matured the T cells show normal PKCζ expression. But at present, we have little understanding of the transient nature of the deficiency and how it relates to other PKC isozymes, addressed now in this study. In the current study, in vitro maturation was initiated by culturing low PKCζ expressing CBTCs with PHA and rhIL-2. The levels of PKCζ and other isozymes were followed over 7 days using isozyme specific antibodies and flow cytometry. PKCζ expression was increased by 2.5 h with further increases by 24h, suggesting ‘normalization’ occurs very early in the T cell maturation process. Of the other isozymes tested only β2, δ, μ, ζ, λ/i were low in CBTCs, also normalizing within 24 h. Only CBTC PKCζ isozyme levels correlated with cytokine production with a positive correlation with the Th1 cytokines IFN-γ, IL-2 and TNF, and a negative association with Th9 cytokine, IL-9 and IL-10, in CD3+ T cells. Deficiency of PKCζ in CBTCs, therefore, appears transient with normal/high CBTC PKCζ levels associated with a propensity for a Th1 anti-allergy cytokine profile following T cell maturation. Low PKCζ levels may represent a biomarker for risk of allergy development. Defining the period of low expression may also provide a window of opportunity for nutritional/epigenetic/environmental regulation of T cell development.