TY - JOUR
T1 - Cord blood t cells expressing high and low pkcζ levels develop into cells with a propensity to display th1 and th9 cytokine profiles, respectively
AU - Perveen, Khalida
AU - Quach, Alex
AU - McPhee, Andrew
AU - Prescott, Susan L.
AU - Barry, Simon C.
AU - Hii, Charles S.
AU - Ferrante, Antonio
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Low Protein Kinase C zeta (PKCζ) levels in cord blood T cells (CBTC) have been shown to correlate with the development of allergic sensitization in childhood. However, little is known about the mechanisms responsible. We have examined the relationship between the expression of different levels of PKCζ in CBTC and their development into mature T cell cytokine producers that relate to allergy or anti‐allergy promoting cells. Maturation of naïve CBTC was initiated with anti‐ CD3/‐CD28 antibodies and recombinant human interleukin‐2 (rhIL‐2). To stimulate lymphocyte proliferation and cytokine production the cells were treated with Phytohaemagglutinin (PHA) and Phorbol myristate acetate (PMA). Irrespective of the PKCζ levels expressed, immature CBTC showed no difference in lymphocyte proliferation and the production of T helper 2 (Th2) cytokine interleukin‐4 (IL‐4) and Th1 cytokine, interferon‐gamma (IFN‐γ), and influenced neither their maturation from CD45RA+ to CD45RO+ cells nor cell viability/apoptosis. However, upon maturation the low PKCζ expressing cells produced low levels of the Th1 cytokines, IFN‐γ, IL‐2 and tumour necrosis factor‐alpha (TNF), no changes to levels of the Th2 cytokines, IL‐4, IL‐5 and IL‐13, and an increase in the Th9 cytokine, IL‐9. Other cytokines, lymphotoxin‐α (LT‐α), IL‐10, IL‐17, IL‐21, IL‐22 and Transforming growth factor‐beta (TGF‐β) were not significantly different. The findings support the view that low CBTC PKCζ levels relate to the increased risk of developing allergic diseases.
AB - Low Protein Kinase C zeta (PKCζ) levels in cord blood T cells (CBTC) have been shown to correlate with the development of allergic sensitization in childhood. However, little is known about the mechanisms responsible. We have examined the relationship between the expression of different levels of PKCζ in CBTC and their development into mature T cell cytokine producers that relate to allergy or anti‐allergy promoting cells. Maturation of naïve CBTC was initiated with anti‐ CD3/‐CD28 antibodies and recombinant human interleukin‐2 (rhIL‐2). To stimulate lymphocyte proliferation and cytokine production the cells were treated with Phytohaemagglutinin (PHA) and Phorbol myristate acetate (PMA). Irrespective of the PKCζ levels expressed, immature CBTC showed no difference in lymphocyte proliferation and the production of T helper 2 (Th2) cytokine interleukin‐4 (IL‐4) and Th1 cytokine, interferon‐gamma (IFN‐γ), and influenced neither their maturation from CD45RA+ to CD45RO+ cells nor cell viability/apoptosis. However, upon maturation the low PKCζ expressing cells produced low levels of the Th1 cytokines, IFN‐γ, IL‐2 and tumour necrosis factor‐alpha (TNF), no changes to levels of the Th2 cytokines, IL‐4, IL‐5 and IL‐13, and an increase in the Th9 cytokine, IL‐9. Other cytokines, lymphotoxin‐α (LT‐α), IL‐10, IL‐17, IL‐21, IL‐22 and Transforming growth factor‐beta (TGF‐β) were not significantly different. The findings support the view that low CBTC PKCζ levels relate to the increased risk of developing allergic diseases.
KW - Allergy
KW - Cord blood T cells
KW - Cytokines
KW - PKCζ
KW - T cell maturation
KW - Th1 and Th2 subsets
UR - http://www.scopus.com/inward/record.url?scp=85105134577&partnerID=8YFLogxK
U2 - 10.3390/ijms22094907
DO - 10.3390/ijms22094907
M3 - Article
C2 - 34063174
AN - SCOPUS:85105134577
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 9
M1 - 4907
ER -