Vulnerability of allografts to rejection by MHC class II-restricted T-cell receptor transgenic mice
Vulnerability of allografts to rejection by MHC class II-restricted T-cell receptor transgenic mice
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DOI：
10.1097/01.tp.0000064296.65628.6c
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发表时间：
2003-04-27
期刊：
影响因子：
6.2
通讯作者：
Markmann, JF
中科院分区：
文献类型：
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作者：
Lee, MK;Huang, XL;Markmann, JF
背景检查体内活化和功能的CD 4 + T细胞在同种异体移植物的反应，可能会促进我们的排斥反应过程的理解。我们分析了转基因II类限制性CD 4 T细胞排斥皮肤、心脏和胰岛移植的能力。TS 1小鼠具有对病毒血凝素（HA）蛋白的免疫显性表位具有特异性的高频率的CD 4 + T细胞。我们分析了皮肤、心脏和胰岛移植物排斥反应的动力学，包括首次免疫和致敏的TS 1小鼠以及过继转移的TS 1淋巴细胞。心脏移植的排斥反应比皮肤移植更快（平均存活时间，12.9对26.6天），胰岛移植物在TS 1小鼠中无限期存活。这些发现可能部分归因于TS 1小鼠中RA反应细胞的超常频率。为了支持这一点，我们发现过继性转移5 × 105个TS 1淋巴细胞到Balb/c宿主中会对携带RA的皮肤移植产生一致的排斥反应，而心脏移植排斥反应需要更大的数量（3 × 106）。HA特异性T细胞对心脏和皮肤的体内增殖反应被发现是稳健的，并且主要局限于引流淋巴结。我们建立了一种同种异体移植排斥反应模型，其中反应性T细胞和相关移植物抗原被明确定义。羧基荧光素琥珀酰亚胺酯标记的转基因T细胞的连续转移使我们能够在体内观察到心脏和皮肤同种异体移植物的强烈增殖反应，在这两种情况下，这些反应都局限于局部淋巴结。
Background. Examination of the in vivo activation and function of CD4+ T cells in response to allografts may advance our understanding of the rejection process. We analyzed the capacity of transgenic class II-restricted CD4 T cells to reject skin, cardiac, and islet transplants.Methods. TS1 mice possess a high frequency of CD4+ T cells specific for the immunodominant epitope of the viral hemagglutinin (HA) protein. We analyzed the kinetics of rejection of skin, heart, and islet grafts by naive and sensitized TS1 mice and by adoptively transferred TS1 lymphocytes.Results. Rejection of heart transplants was more rapid than skin grafts (mean survival time, 12.9 vs. 26.6 days), and islet grafts survived indefinitely in TS1 mice. These findings may be partly attributable to the supranormal frequency of RA-reactive cells in TS1 mice. In support of this, we found that adoptive transfer of 5x10(5) TS1 lymphocytes to Balb/c hosts effected consistent rejection of RA-bearing skin transplants, whereas a significantly greater number (3x10(6)) was required for heart transplant rejection. The in vivo proliferative response of HA-specific T cells to heart and skin was found to be robust and predominantly localized to the draining lymph nodes.Conclusion. We developed a model of allograft rejection in which the responding T cells and relevant graft antigen are specifically defined. Adoptive transfer of carboxy-fluorescein succinimidyl ester-labeled transgenic T cells allowed us to visualize a robust proliferative response in vivo to heart and skin allografts, which,in both cases was localized to regional lymph nodes.