Divergent response profile in activated cord blood T cells from first-born child implies birth-order-associated in utero immune programming.
BACKGROUND
First-born children are at higher risk of developing 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.


METHODS
Purified cord blood T cells were polyclonally activated with anti-CD3-/anti-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 the supernatants.


RESULTS
IL-10 secretion (P = 0.007) and CD25 expression on CD4(+) helper T cells (P = 0.0003) in the activated cord blood T cells were selectively reduced in first-born children, while the percentage of circulating CD4(+) CD25(+) cord blood T cells was independent of birth order.


CONCLUSIONS
First-born infants display a reduced anti-inflammatory profile in T cells at birth. This possible in utero 'birth-order' T-cell programming may contribute to later development of immune-mediated diseases by increasing overall immune reactivity in first-born children as compared to younger siblings.
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
M
M
Kragh
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
J M
JM
Larsen
Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
A H
AH
Thysen
Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
M A
MA
Rasmussen
Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
H M
HM
Wolsk
Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
H
H
Bisgaard
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
S
S
Brix
D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007154:Immune System Diseases / Q000209:etiology / Q000378:metabolism; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D015703:Antigens, CD; D015415:Biomarkers; D016207:Cytokines
T cells; immune regulation; in utero programming; neonates; parity number