Developing Patterns of T Cell Memory to Environmental Allergens in the First Two Years of Life

Abstract

Several recent studies have demonstrated cord blood mononuclear cell (CBMC) proliferation in response to food and inhalant allergens, suggesting that initial T-cell-priming may occur in utero. The findings below from an ongoing prospective study on 60 subjects provide initial information on the nature of accompanying T cell cytokine responses. We demonstrate CBMC proliferation following culture with house dust mite and ovalbumin (OVA) in 47 and 42% of subjects, respectively, compared to an overall rate of 3% for tetanus toxoid; the frequencies of these responses were comparable in neonates with and without atopic family history (FH). With the exception of IL-10, analysis of cytokine responses in allergen-stimulated cultures of CBMCs required the use of semiquantitative RT-PCR, which revealed low-level IL-4 and/or IL-5 mRNA production, in particular a 50% IL-5 response rate to OVA in FH-positive neonates. IFN-γ responses were less frequent and required higher PCR cycle numbers for detection. Preliminary analysis of culture supernatants from a subgroup of CBMCs indicate high-level allergen-specific IL-10 responses in both FH-negative and -positive subjects, detectable by ELISA. Parallel PCR studies on MCs from 27 children (mean age 18 months) indicated a clear segregation at this age on the basis of FH, with Th0-like or mixed Th1/Th2 responses (IL-5 plus IFN-γ) which were mainly restricted to the FH-positive group.