Abstract
While immunodeficiency of immaturity of the neonate has been considered important as the basis for unusual susceptibility to infection, it has also been recognized that the ability to progress from an immature Th2 cytokine predominance to a Th1 profile has relevance in determining whether children will develop allergy, providing an opportunity for epigenetic regulation through environmental pressures. However, this notion remains relatively unexplored. Here, we present evidence that there are two major control points to explain the immunodeficiency in cord blood (CB) T-cells, a deficiency in interleukin (IL)-12 (IL-12) producing and IL-10 overproducing accessory cells, leading to a decreased interferon γ (IFNγ) synthesis and the other, an intrinsic defect in T-cell protein kinase C (PKC) ζ (PKCζ) expression. An important finding was that human CB T-cells rendered deficient in PKCζ, by shRNA knockdown, develop into low tumour necrosis factor α (TNFα) and IFNγ but increased IL-13 producing cells. Interestingly, we found that the increase in PKCζ levels in CB T-cells caused by prenatal supplementation with fish oil correlated with modifications of histone acetylation at the PKCζ gene (PRKCZ) promoter. The data demonstrate that PKCζ expression regulates the maturation of neonatal T-cells into specific functional phenotypes and that environmental influences may work via PKCζ to regulate these phenotypes and disease susceptibility.
Highlights
The distinct functional characteristics of neonatal T-cells compared with those of adults are understood to reflect an adaptive immune profile in response to the unique developmental context of intrauterine life [1,2,3,4,5,6,7,8,9,10]
While the prime focus of this work was to examine the role of PKC ζ (PKCζ) in cord blood (CB) T-cell development-specific functional phenotype, studies on IL-12 and IL-10 were conducted to provide a comparison with the T-cell deficiency per se
The production of interferon γ (IFNγ) by human CB mononuclear cell (CBMC) was of the order of 5% of that observed with peripheral blood mononuclear cell (PBMC) from adults when accessory cells were stimulated with LPS (Figure 1A, left panel)
Summary
The distinct functional characteristics of neonatal T-cells compared with those of adults are understood to reflect an adaptive immune profile in response to the unique developmental context of intrauterine life [1,2,3,4,5,6,7,8,9,10]. Rather than in a simple linear manner from immaturity to maturity, the immune system appears to develop in distinct functional waves that serve different purposes at different developmental stages [3,4,11,12,13,14]. T-cells undergo a series of age-related changes to eventually achieve the regulated Th1-dominant ‘mature’ patterns of response observed in adult life [15,16,17,18,19]. Differences in T-cell function, evident both at birth and in trajectory of postnatal maturation, have been shown to precede the development of allergic inflammation [18,20,21].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
