CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells.
CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells.
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DOI：
10.1084/jem.187.10.1555
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发表时间：
1998-05-18
期刊：
影响因子：
--
通讯作者：
Pardoll DM
中科院分区：
文献类型：
--
作者：
Adler AJ;Marsh DW;Yochum GS;Guzzo JL;Nigam A;Nelson WG;Pardoll DM
T细胞对实质自身抗原的耐受被认为是由T细胞与其在实质细胞上表达的同源肽 - 主要组织相容性复合体（MHC）配体相遇所诱导的，实质细胞缺乏适当的共刺激功能。我们使用了一个模型系统，在该系统中，将初始T细胞受体（TCR）转基因的血凝素（HA）特异性CD4 + T细胞过继转移到实质细胞上表达HA作为自身抗原的小鼠体内。转移后，HA特异性T细胞呈现出一种表明TCR参与的表型，并在功能上产生耐受。然而，T细胞耐受不是由实质细胞上表达的肽 - MHC复合物所诱导。相反，耐受诱导需要HA由骨髓（BM）来源的细胞呈递。这些结果表明，对实质自身抗原的耐受诱导需要转移到一个骨髓来源的抗原呈递细胞，该细胞以一种致耐受的方式将抗原呈递给T细胞。
T cell tolerance to parenchymal self-antigens is thought to be induced by encounter of the T cell with its cognate peptide–major histocompatibility complex (MHC) ligand expressed on the parenchymal cell, which lacks appropriate costimulatory function. We have used a model system in which naive T cell receptor (TCR) transgenic hemagglutinin (HA)-specific CD4+ T cells are adoptively transferred into mice expressing HA as a self-antigen on parenchymal cells. After transfer, HA-specific T cells develop a phenotype indicative of TCR engagement and are rendered functionally tolerant. However, T cell tolerance is not induced by peptide–MHC complexes expressed on parenchymal cells. Rather, tolerance induction requires that HA is presented by bone marrow (BM)–derived cells. These results indicate that tolerance induction to parenchymal self-antigens requires transfer to a BM-derived antigen-presenting cell that presents it to T cells in a tolerogenic fashion.
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