Deficient cytokine response of human allergen-specific T lymphocytes from humanized SCID mice and reconstitution by professional antigen-presenting cells

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:105

Article

Jarman, ER ; Perschke, K ; Montermann, E ; Herz, U ; Renz, H ; Knop, J ; Reske-Kunz, AB

关键词: allergy;    anergy;    hu-PBL-SCID;    IgE;   

DOI  :  10.1067/mai.2000.105320

来源: Elsevier

【 摘 要 】

Background: Hu-PBL-SCID mice generated by the transfer of PBMCs from atopic individuals may provide a physiologic in vivo model for investigating human responses to allergens and potential approaches toward immunotherapy. Objective: This study was undertaken to investigate the functional activity and cytokine profile of human allergen-reactive T lymphocytes isolated from hu-PBL-SCID mice. Methods: PBMCs from allergic individuals vc ere coinjected with allergen into SCID mice. Human lymphocyte migration and phenotype were established by reverse transcription-PCR and immunohistochemistry; IgE levels in sera were determined, and the frequency of allergen-reactive cytokine-producing T lymphocytes was established. Results: After immunization with allergen, specific IgE levels in hu-PBL-SCID sera were comparable with levels in donor sera. Although the majority of lymphocytes remained in the peritoneum, significant numbers of T lymphocytes were located in the spleen, where human IL-4, IL-5, and IFN-gamma messenger RNA expression was detected after stimulation with PHA and phorbol myristate acetate, Failure to induce cytokine production by human T lymphocytes isolated from the peritoneum and spleen of hu-PBL-SCID mice by allergen was reversed by stimulating with allergen in the presence of exogenously added IL-2 and antigen-presenting cells (APC), particularly CD14(+) monocytes. Under these conditions, allergen-reactive T cells expressed a T(H)2-like phenotype. Conclusions: These data suggest that, after initial activation and induction of antibody production, human T lymphocytes enter a state of unresponsiveness, arising from a loss of human professional APC, in hu-PBL-SCID mice. The use of hu-PBL-SCID mouse models in studies on therapeutic approaches for allergy may benefit from the additional transfer of human professional APC.

【 授权许可】

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