In utero priming of allergen‐specific helper T cells

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Abstract
Background Allergic diseases are major health problems in developed countries. Cord blood mononuclear cells (CBMC) at birth can proliferate after stimulation with allergen and this has led to the widespread view that the sensitization of the fetal immune system by allergens is a key determinant in establishing immunological bias towards allergy. However, the notion that the immune system can be primed by allergen in utero remains unproven. Determination of the CD45 isoform of responding T helper cells is an established method of determining the activation status of responding T helper cells because unsensitized cells express CD45RAhigh and previously sensitized cells CD45ROhigh. Objective To determine if sensitization of allergen‐specific T helper cells can occur in utero by determining the CD45 isoform of CBMC proliferating in response to allergen. Methods CBMC proliferative responses were measured after stimulation in culture with a panel of allergens, mitogen and control antigen. To ascertain whether any responding T helper cells had been primed in utero, depletion experiments established whether they carried the CD45ROhigh marker of previous activation or the CD45RAhigh marker of unstimulated T cells. Results CBMC from a high proportion of 223 randomly selected neonates were stimulated to proliferate in vitro by allergens, with 76% responding to timothy grass pollen. In 50% of such responses to timothy grass, the CD45 isoform of the T cells that proliferate indicated that they had been previously activated. However, the remaining 50% of responses to timothy grass were mediated by previously unstimulated T cells. Proliferative responses mediated by CBMC sensitized in utero tended to be greater in magnitude than those mediated by unsensitized cells (P = 0.08). Seventy‐five per cent of CBMC samples proliferated after stimulation with mycobacterial PPD and, as in BCG‐vaccinated adults, all such CBMC proliferative responses at birth were predominately mediated by sensitized cells. Conclusion Allergen‐ and antigen‐specific Th cells can be primed in utero.