TY - JOUR
T1 - Divergent Response Profile in Activated Cord Blood T cells from First-born Child Implies Birth-order-associated in Utero Immune Programming
AU - Kragh, Marie
AU - Larsen, Jeppe Madura
AU - Thysen, Anna Hammerich
AU - Rasmussen, Morten Arendt
AU - Wolsk, Helene Mygind
AU - Bisgaard, Hans Flinker
AU - Pedersen, Susanne Brix
PY - 2016
Y1 - 2016
N2 - Background: First-born children are at higher risk for development of a range of immune-mediated diseases. The underlying mechanism of ‘birth-order-effects’ on disease risk is largely unknown, but in utero programming of the child's immune system may play a role.
Objective:
We studied the association between birth-order and the functional response of stimulated cord blood T cells.
Method:
Purified cord blood T cells were polyclonally activated with anti-CD3/CD28-coated beads in a subgroup of 28 children enrolled in the COPSAC2010 birth cohort. Expression levels of seven activation markers on helper and cytotoxic T cells as well as the percentage of CD4+CD25+ T cells were assessed by flow cytometry. Production of IFN-γ, TNF-α, IL-17, IL-4, IL-5, IL-13 and IL-10 was measured in supernatants.
Results:
IL-10 secretion (P = 0.007) and CD25 expression on CD4+ helper T cells (P = 0.0003) in activated cord blood T cells were selectively reduced in first-born children, while the percentage of CD4+CD25+ cord blood T cells was independent of birth-order.
Conclusion:
First-born infants display a reduced anti-inflammatory profile in T cells at birth. This possible in utero ‘birth-order’ T cell programing may contribute to later development of immune-mediated diseases by increasing overall immune reactivity in first-born children as compared to younger siblings.
AB - Background: First-born children are at higher risk for development of a range of immune-mediated diseases. The underlying mechanism of ‘birth-order-effects’ on disease risk is largely unknown, but in utero programming of the child's immune system may play a role.
Objective:
We studied the association between birth-order and the functional response of stimulated cord blood T cells.
Method:
Purified cord blood T cells were polyclonally activated with anti-CD3/CD28-coated beads in a subgroup of 28 children enrolled in the COPSAC2010 birth cohort. Expression levels of seven activation markers on helper and cytotoxic T cells as well as the percentage of CD4+CD25+ T cells were assessed by flow cytometry. Production of IFN-γ, TNF-α, IL-17, IL-4, IL-5, IL-13 and IL-10 was measured in supernatants.
Results:
IL-10 secretion (P = 0.007) and CD25 expression on CD4+ helper T cells (P = 0.0003) in activated cord blood T cells were selectively reduced in first-born children, while the percentage of CD4+CD25+ cord blood T cells was independent of birth-order.
Conclusion:
First-born infants display a reduced anti-inflammatory profile in T cells at birth. This possible in utero ‘birth-order’ T cell programing may contribute to later development of immune-mediated diseases by increasing overall immune reactivity in first-born children as compared to younger siblings.
KW - Parity number
KW - Neonates
KW - T cells
KW - Immune regulation
KW - In utero programming
U2 - 10.1111/all.12799
DO - 10.1111/all.12799
M3 - Journal article
C2 - 26505887
VL - 71
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
SN - 0105-4538
IS - 3
ER -