ANTIGEN PRESENTING FUNCTION OF CLASS-II MHC EXPRESSING PANCREATIC BETA-CELLS
ANTIGEN PRESENTING FUNCTION OF CLASS-II MHC EXPRESSING PANCREATIC BETA-CELLS
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DOI：
10.1038/336476a0
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发表时间：
1988-12-01
期刊：
影响因子：
64.8
通讯作者：
HEBERKATZ, E
中科院分区：
文献类型：
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作者：
MARKMANN, J;LO, D;HEBERKATZ, E
小鼠中的II类主要组织相容性复合体（MHC）基因表达通常限于胸腺上皮和骨髓来源的细胞，例如B淋巴细胞和巨噬细胞/树突状细胞谱系（MHC/DC）的细胞。携带II类B淋巴细胞和MHC/DC具有抗原呈递细胞（APC）功能;即，它们可以刺激对抗原加MHC或单独的外源MHC反应的T淋巴细胞。为了评估非骨髓来源的细胞是否可以获得APC功能并通过表达II类分子引起移植物排斥，我们研究了表达外源II类（I-E）分子的转基因胰岛β细胞。在体内，将I-E+转基因胰岛移植到I-E-幼稚宿主中不会被排斥，除非宿主通过注射I-E+脾细胞引发。在体外，I-E+ β细胞不能刺激对I-E加肽抗原反应的T淋巴细胞。特别地，它们在T细胞中诱导抗原特异性无应答性。我们建议，非淋巴样细胞上的II类表达可能作为一种胸腺外机制，以维持自身耐受。
Class II major histocompatibility complex (MHC) gene expression in the mouse is generally limited to thymic epithelium and bone marrow-derived cells such as B lymphocytes and cells of the macrophage/dendritic cell lineage (MØ/DC). Class II-bearing B lymphocytes and MØ/DC possess antigen presenting cell (APC) function; that is, they can stimulate T lymphocytes reactive to either antigen plus MHC or foreign MHC alone. To assess whether non-bone-marrow-derived cells can acquire APC function and elicit graft rejection through expression of class II, we studied transgenic pancreatic islet beta cells that express a foreign class II (I-E) molecule.In vivo, grafts of I-E+transgenic islets into I-E-naive hosts are not rejected unless the host is primed by an injection of I-E+spleen cells.In vitro, the I-E+beta cells are unable to stimulate T lymphocytes reactive to I-E plus a peptide antigen. Paradoxically, they induce antigen specific unresponsiveness in the T cells. We propose that expression of class II on non-lymphoid cells may serve as an extrathymic mechanism for maintaining self tolerance.