Effects of T cell frequency and graft size on transplant outcome in mice
Effects of T cell frequency and graft size on transplant outcome in mice
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DOI：
10.4049/jimmunol.172.1.240
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发表时间：
2004-01-01
影响因子：
4.4
通讯作者：
Heeger, PS
中科院分区：
文献类型：
--
作者：
He, CS;Schenk, S;Heeger, PS
决定移植物反应性T淋巴细胞是否发育成能够介导器官破坏的效应细胞的特征还不是很清楚。为了调查参与这一过程的潜在因素，我们首先证实，雌性受体小鼠强烈排斥微小的、不同于Ag的雄性皮肤，但不排斥心脏移植。尽管结果不同，心脏和皮肤移植诱导的抗供者T细胞反应的大小、特异性和细胞因子谱相似。心脏移植物引发的T细胞瞬间渗入移植物，最终导致慢性移植物血管病变的发生。通过预敏化或使用TCR(CD8(+)抗癌)转基因受体增加供者反应性T细胞的频率并不会导致急性排斥反应，但会加速血管病变的速度和严重程度。令人惊讶的是，将供者心脏的组织质量减少50%会导致这些较小移植物的急性排斥反应，而不会增加受者体内抗供体效应器T细胞的频率。在互补性研究中，在单个受者身上放置一到两个男性皮肤移植物并不影响诱导的抗恶性T细胞谱系的频率或细胞因子谱。尽管如此，接受单次皮肤移植的人强烈排斥移植的皮肤，而接受两次皮肤移植的人则没有。这些结果为移植血管病变的发病机制提供了新的见解，并通过强调移植反应性T细胞免疫的效率在很大程度上受到其在效应期遇到的组织负荷的影响这一新概念，为小鼠皮肤和心脏移植结果的差异提供了解释。
The features that determine whether graft-reactive T lymphocytes develop into effector cells capable of mediating organ destruction are not well understood. To investigate potential factors involved in this process, we first confirmed that female recipient mice acutely rejected minor Ag-disparate male skin, but not heart transplants. Despite this difference in outcome, heart and skin transplantation induced antidonor T cell responses of similar magnitude, specificity, and cytokine profile. The heart-graft-primed T cells transiently infiltrated the graft and ultimately induced the development of chronic transplant vasculopathy. Increasing the frequency of donor-reactive T cells by presensitization or by using TCR (CD8(+) antimale)-transgenic recipients did not mediate acute rejection but accelerated the pace and severity of the vasculopathy. Surprisingly, decreasing the tissue mass of the donor heart by 50% resulted in acute rejection of these smaller grafts without increasing the frequency of antidonor effector T cells in the recipients. In complementary studies, placement of one or two male skin grafts on a single recipient did not affect the frequency or cytokine profile of the induced antimale T cell repertoire. Nonetheless, the recipients of single grafts acutely rejected the transplanted skin while the recipients of two skin grafts did not. These results provide new insight into the pathogenesis of transplant vasculopathy and provide an explanation for the difference in outcome between murine skin and heart transplants by highlighting the novel concept that the efficiency of transplant-reactive T cell immunity is heavily influenced by the tissue burden it encounters at the effector stage.