Divergent response profile in activated cord blood T cells from first-born child implies birth-order-associatedin uteroimmune programming

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Abstract

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.

Method:

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.

Conclusion:

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.

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