Induction of specific T cell tolerance by Fas ligand-expressing antigen-presenting cells.
Induction of specific T cell tolerance by Fas ligand-expressing antigen-presenting cells.
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DOI：
10.4049/jimmunol.162.3.1423
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发表时间：
1999-02
影响因子：
4.4
通讯作者：
Huang-Ge Zhang;X. Su;Di Liu;Weimin Liu;Pingar Yang;Zheng Wang;C. K. Edwards;Horst Bluethmann;J. Mountz;Tong Zhou
中科院分区：
文献类型：
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作者：
Huang-Ge Zhang;X. Su;Di Liu;Weimin Liu;Pingar Yang;Zheng Wang;C. K. Edwards;Horst Bluethmann;J. Mountz;Tong Zhou
Fas 和 Fas 配体的自分泌相互作用导致活化 T 细胞凋亡，这一过程对于维持外周 T 细胞耐受性至关重要。 Fas 配体与 T 细胞的旁分泌相互作用也可能在维持耐受性中发挥重要作用，因为 Fas 配体可以创建免疫豁免位点并通过诱导 T 细胞凋亡来防止移植物排斥。我们推测表达Fas配体的APC可能在将Ag呈递给T细胞期间直接诱导T细胞凋亡，从而诱导Ag特异性、全身性T细胞耐受。在这里，我们表明，用表达 Fas 配体的 H-2b APC 处理 H-2k 小鼠可诱导对同种抗原的深度特异性 T 细胞无反应，而用表达 Fas 配体的 H-2Db/H-Y APC 处理 H-2Db/H-Y TCR 转基因雌性小鼠可诱导对 H-Y Ag 特异性的深度 T 细胞无反应。这种全身性 T 细胞耐受性的诱导需要 APC 上 Fas 配体的表达以及 T 细胞上 Fas 的表达。耐受性仅限于 APC 呈现的 Ag。由表达 Fas 配体的 APC 介导的 Ag 特异性外周 T 细胞的快速而深度的克隆删除有助于诱导耐受。这些发现表明，表达 Fas 配体的 APC 可以诱导 Ag 特异性 T 细胞耐受，并表明 APC 在诱导 T 细胞凋亡中具有新功能。此外，它们还提出了一种用于治疗移植物排斥和自身抗原特异性自身免疫性疾病的新型免疫干预策略。
Autocrine interaction of Fas and Fas ligand leads to apoptosis of activated T cells, a process that is critical for the maintenance of peripheral T cell tolerance. Paracrine interactions of Fas ligand with T cells also may play an important role in the maintenance of tolerance, as Fas ligand can create immune-privileged sites and prevent graft rejection by inducing apoptosis in T cells. We surmised that APCs that express Fas ligand might directly induce apoptosis of T cells during presentation of Ag to the T cells, thus inducing Ag-specific, systemic T cell tolerance. Here, we show that profound, specific T cell unresponsiveness to alloantigen was induced by treatment of H-2k mice with H-2b APCs that expressed Fas ligand and that profound T cell unresponsiveness specific for the H-Y Ag was induced by treatment of H-2Db/H-Y TCR transgenic female mice with H-2Db/H-Y APCs that expressed Fas ligand. The induction of this systemic T cell tolerance required the expression of Fas ligand on the APCs as well as the expression of Fas on the T cells. The tolerance was restricted to the Ag presented by the APCs. The rapid and profound clonal deletion of the Ag-specific, peripheral T cells mediated by the Fas ligand-expressing APCs contributed to the induction of tolerance. These findings demonstrate that Ag-specific T cell tolerance can be induced by APCs that express Fas ligand and suggest a novel function for APCs in the induction of T cell apoptosis. Furthermore, they indicate a novel immunointervention strategy for treatment of graft rejection and autoantigen-specific autoimmune diseases.