由Der p 1刺激的树突状细胞和重组白细胞介素-12在特应性和健康受试者中引发的辅助性T细胞反应。

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

作者信息

De Wit D, Amraoui Z, Vincart B, Michel O, Michils A, Van Overvelt L, Willems F, Goldman M

机构信息

Laboratory of Experimental Immunology and Centre de recherche Inter-Universitaire en Vaccinologie (C.R.I.V), Universite Libre de Bruxelles, Brussels.

出版信息

J Allergy Clin Immunol. 2000 Feb;105(2 Pt 1):346-52. doi: 10.1016/s0091-6749(00)90086-1.

DOI:10.1016/s0091-6749(00)90086-1

PMID:10669857

Abstract

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 rIL-12.

摘要

背景

环境过敏原，如屋尘螨1组抗原（Der p 1），可在特应性患者中诱导T（H2）型反应，而健康个体对相同抗原产生T（H1）型反应。由于树突状细胞（DCs）能有效合成白细胞介素12（IL-12），它们是T（H1）型免疫反应的有效诱导剂。

目的

我们试图确定DCs是否会使特应性个体的过敏原特异性T（H2）型反应发生偏移。

方法

将来自健康供体或特应性个体的纯化CD4（+）T细胞，在不存在或存在重组（r）IL-12的情况下，与源自外周血单核细胞（PBMCs）且用Der p 1脉冲处理的DCs一起培养。通过酶联免疫吸附测定（ELISA）检测DC-T细胞共培养上清液中的IL-5和干扰素-γ（IFN-γ）。

结果

来自健康供体的纯化CD4（+）T细胞对用Der p 1脉冲处理的DCs产生T（H1）型反应，培养上清液中IFN-γ水平较高表明了这一点。相比之下，来自特应性供体的CD4（+）T细胞呈现T（H2）型特征，其IL-5水平高而IFN-γ水平低。向DC-T细胞共培养物中添加rIL-12（10纳克/毫升）导致特应性患者的Der p 1特异性CD4（+）T细胞分泌IFN-γ，而其IL-5的产生未受抑制。通过胞内染色后的流式细胞术，我们发现IFN-γ和IL-5由不同的CD4（+）T细胞亚群分泌。