ANTIGEN PRESENTATION BY KERATINOCYTES INDUCES TOLERANCE IN HUMAN T-CELLS
ANTIGEN PRESENTATION BY KERATINOCYTES INDUCES TOLERANCE IN HUMAN T-CELLS
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DOI：
10.1002/eji.1830200904
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发表时间：
1990-09-01
影响因子：
5.4
通讯作者：
LECHLER, R
中科院分区：
文献类型：
--
作者：
BAL, V;MCINDOE, A;LECHLER, R
产生白细胞介素2（IL 2）的T淋巴细胞识别抗原可导致两种不同的结果，这取决于抗原呈递细胞的性质。识别由专门的抗原呈递细胞呈递的抗原导致T细胞活化;相反，缺乏“辅助功能”的细胞的抗原呈递可导致特异性无应答状态，其特征在于不能产生IL 2。我们在该研究中已经表明，HLA-DR 1/4限制的流感血凝素特异性T细胞克隆与由干扰素-γ-呈递的特异性肽的共培养，诱导的DR 4受限，因为它需要将T细胞克隆与表达适当DR类型（DR 4Dw 14）的角质形成细胞预孵育。T细胞耐受性的诱导也是抗原特异性的;克隆与不相关肽的预孵育没有导致抑制。此外，细胞与细胞的接触似乎是必要的，并且加入来自干扰素-γ-的上清液，诱导的角质形成细胞没有引起任何抑制。这种现象可能与移植培养的角质形成细胞的免疫原性和主要组织相容性复合物II类诱导对非骨髓来源的细胞的影响有关。角质形成细胞等细胞对组织特异性自身抗原的呈递可能提供了一种避免而不是刺激局部炎症反应背景下自身免疫反应的机制。
Antigen recognition by interleukin 2 (IL 2)-producing T lymphocytes can lead to two distinct outcomes, depending on the nature of the antigen-presenting cell. Recognition of antigen presented by specialized antigen-presenting cells leads to T cell activation; in contrast, antigen presentation by cells which lack "accessory function" can lead to a state of specific nonresponsiveness, which is characterized by a failure to produce IL 2. We have shown in this study that co-culture of an HLA-DR1/4 restricted, influenza hemagglutinin-specific T cell clone with a specific peptide presented by interferon-.gamma.-induced DR4 restricted, in that it required pre-incubation of the T cell clone with keratinocytes expressing an appropriate DR type (DR4Dw14). The induction of T cell tolerance was also antigen specific; no inhibition resulted from pre-incubation of the clone with an irrelevant peptide. Furthermore cell to cell contact appeared to be necessary, and the addition of supernatant from interferon-.gamma.-induced keratinocytes did not cause any inhibition. This phenomenon may have relevance to the immunogencity of transplanted cultured keratinocytes and to the effects of major histocompatibility complex class II induction on non-bone marrow-derived cells. Presentation of tissue-specific autoantigens by cells such as keratinocytes may provide a mechanism of avoiding, rather than stimulating, autoimmune reactions in the context of a local inflammatory response.