TOLERANCE IN TRANSGENIC MICE EXPRESSING CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX ON PANCREATIC ACINAR-CELLS
TOLERANCE IN TRANSGENIC MICE EXPRESSING CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX ON PANCREATIC ACINAR-CELLS
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DOI：
10.1084/jem.170.1.87
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发表时间：
1989-07-01
影响因子：
15.3
通讯作者：
BRINSTER, RL
中科院分区：
文献类型：
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作者：
LO, D;BURKLY, LC;BRINSTER, RL
为了研究对淋巴系统细胞不表达的抗原的耐受性的性质，将II类MHC I-E的表达靶向于转基因小鼠中胰腺外分泌腺的腺泡细胞（弹性蛋白酶[EL]-I-E）。尽管在EL-I-E转基因小鼠的胸腺中没有可检测到的I-E，但胸腺细胞和外周T淋巴细胞都对I-E耐受，并且胰腺没有自身免疫浸润。非耐受性T细胞过继转移到辐射或T-耗尽的转基因小鼠迅速破坏I-E+组件的胰腺，然而，过继转移的非耐受性T淋巴细胞到非辐射转基因小鼠不。这些结果表明，在转基因小鼠的耐受性是通过一些外周耐受机制。然而，进一步的研究表明，在转基因小鼠的耐受性不是由特定的Ts细胞。例如，体外和体内的细胞混合实验都未能揭示显性无反应性。 此外，注射到另外未经操作的EL-I-E小鼠中的非耐受性T细胞可以原位引发（通过注射I-E+脾细胞）以破坏I-E+腺泡细胞。
To study the nature of tolerance to antigens not expressed by cells of the lymphoid system, expression of class II MHC I-E was targeted to the acinar cells of the exocrine pancreas in transgenic mice (elastase [EL]-I-E). Despite the absence of detectable I-E in the thymus of EL-I-E transgenic mice, both thymocytes and peripheral T lymphocytes were tolerant to I-E, and the pancreas was free of autoimmune infiltrates. Nontolerant T cells adoptively transferred into irradiated or T-depleted transgenic mice rapidly destroy the I-E+ components of the pancreas; however, adoptive transfer of nontolerant T lymphocytes into nonirradiated transgenic mice do not. These results suggest that tolerance in transgenic mice is maintained by some peripheral tolerance mechanism. However, further studies indicate that tolerance in transgenic mice is not maintained by specific Ts cells. For example, cell mixing experiments both in vitro and in vivo fail to reveal dominant unresponsiveness. Furthermore, nontolerant T cells injected into otherwise unmanipulated EL-I-E mice can be primed in situ (by injections of I-E+ spleen cells) to destroy the I-E+ acinar cells.