Geiger T, Soldevila G, Flavell R A
Section of Immunobiology, Yale University School of Medicine, New Haven, CT.
J Immunol. 1993 Dec 15;151(12):7030-7.
The qualities of a peripheral Ag that determine whether T cells will be tolerant of or responsive to it are poorly understood. To approach this problem, we studied the T cell response in a line of transgenic mice selectively expressing an oncoprotein in the islets of Langerhans. The SV40 large tumor Ag (SV40-T) is directed to islet beta-cells in Rip1-Tag3 (RT3) mice by a hybrid insulin promoter-SV40-T construct. Ag is first detected on these cells between 10 and 12 wk after birth. RT3 mice were bred with mice expressing a transgenic rearranged TCR recognizing SV40-T in the context of the class I MHC molecule, H-2Kk. T cell response in the resultant RT3/TCR-double transgenic mice was then analyzed. T cells are fully responsive to SV40-T in RT3/TCR-transgenic mice, and T cells infiltrate the islets of both RT3 and RT3/TCR-transgenic mice. This work demonstrates that T cells may remain responsive to self-Ag expressed outside the thymus, and that this responsiveness may result in autoimmunity. The developmentally delayed expression or the oncogenic nature of SV40-T in the RT3-transgenic mice may be important in determining this T cell response.
对于决定T细胞对其产生耐受还是产生应答的外周抗原的特性，人们了解甚少。为了解决这个问题，我们研究了在胰岛中选择性表达一种癌蛋白的转基因小鼠品系中的T细胞应答。通过杂交胰岛素启动子-SV40-T构建体，SV40大肿瘤抗原（SV40-T）被导向Rip1-Tag3（RT3）小鼠的胰岛β细胞。出生后10至12周之间首次在这些细胞上检测到抗原。将RT3小鼠与表达在I类MHC分子H-2Kk背景下识别SV40-T的转基因重排TCR的小鼠进行杂交。然后分析所得的RT3/TCR双转基因小鼠中的T细胞应答。在RT3/TCR转基因小鼠中，T细胞对SV40-T完全有应答，并且T细胞浸润RT3和RT3/TCR转基因小鼠的胰岛。这项工作表明，T细胞可能对外周表达的自身抗原有应答，并且这种应答可能导致自身免疫。RT3转基因小鼠中SV40-T发育延迟的表达或致癌性质在决定这种T细胞应答中可能很重要。
