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.


CONCLUSIONS
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 rIL-12.
De Wit
D
D
Laboratory of Experimental Immunology and Centre de recherche Inter-Universitaire en Vaccinologie (C.R.I.V), Universite Libre de Bruxelles, Brussels.
Amraoui
Z
Z
Vincart
B
B
Michel
O
O
Michils
A
A
Van Overvelt
L
L
Willems
F
F
Goldman
M
M
D000485:Allergens / Q000276:immunology*; D039741:Antigens, Dermatophagoides; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000276:immunology*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology* / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
D000485:Allergens; D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D015848:Interleukin-5; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma