Helper T-cell responses elicited by Der p 1-pulsed dendritic cells and recombinant IL-12 in atopic and healthy subjects

Background: Environmental allergens, such as Dermatophagoides pteronyssinus group 1 antigen (Der p 1), induce T-H2-type responses in atopic patients, whereas healthy individuals have T-H1-type responses to the same antigens, Because of their efficient synthesis of IL-12, dendritic cells (DCs) are potent inducers of T-H1-type immune responses. Objective: We sought to determine whether DCs would skew allergen-specific T-H2-type responses from atopic individuals. Methods: Purified CD4(+) T cells from healthy donors or atopic individuals were cultured in the absence or presence of recombinant (r)IL-12 with DCs derived from PBMCs and pulsed with Der p 1. Supernatants of DC-T cell cocultures were assayed by ELISA for IL-5 and IFN-gamma. Results: A T-H1-type response developed in purified CD4(+) T cells from healthy donors in response to Der p 1-pulsed DCs, as indicated by high levels of IFN-gamma in culture supernatants. In contrast, CD4(+) T cells from atopic donors displayed a T-H2-type profile characterized by high levels of IL-5 and low levels of IFN-gamma. The addition of rIL-12 (10 ng/mL) to DC-T cell cocultures resulted in the induction of IFN-gamma secretion by Der p 1-specific CD4(+) T cells from atopic patients, whereas their production of IL-5 was not inhibited. Using flow cytometry after intracytoplasmic staining, we found that IFN-gamma and IL-5 were secreted by distinct CD4(+) T-cell subpopulations. Conclusion: The cytokine profile of Der p 1-specific T-H2-like cells from atopic individuals is maintained when the allergen is presented by DCs, even in the presence of exogenous IL-12.