Zhao Y, Barth R N, Swenson K, Pearson D A, Sykes M
Bone Marrow Transplantation Section, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
Xenotransplantation. 1998 Feb;5(1):99-104. doi: 10.1111/j.1399-3089.1998.tb00015.x.
Mouse CD4+ T cells efficiently develop in fetal pig thymus (FP THY) grafts and repopulate the periphery of T cell and NK cell-depleted, thymectomized (ATX) mice. However, efficient peripheral repopulation of mouse CD8+ T cells does not occur in these mice. We have therefore evaluated the maturation and function of mouse CD8 single positive (SP) thymocytes in fetal pig thymus and liver fragment (FP THY LIV) grafts. Phenotypic maturity, as measured by upregulated expression of TCR, class I MHC, and Qa-2, and downregulated expression of heat stable antigen (HSA) on CD8 SP cells in FP THY grafts, was similar to that in host thymi of euthymic control mice. Cytolytic T lymphocyte (CTL) activity of thymocytes from FP THY grafts was similar to that of thymocytes from host thymi of euthymic mice, indicating that functional maturation of CD8 SP cells had taken place in the grafts. Furthermore, similarly efficient deletion of V beta 5.1/5.2+ and V beta 11+ CD8 SP cells was observed in FP THY grafts as in host thymi of euthymic control mice. Similar percentages of V beta 6, V beta 7, and V beta 8.1/8.2 expressing cells were also detected among CD8 SP cells in FP THY grafts and host thymi of euthymic controls. Together, our results suggest that normal positive and negative selection occurs, and that mouse CD8+ cells can undergo normal functional and phenotypic maturation in FP THY grafts. Thus, other explanations must be sought for the failure of CD8+ cells to repopulate the peripheral lymphoid tissues of ATX, T cell-depleted, pig THY/LIV-grafted mice.
小鼠CD4⁺ T细胞在胎猪胸腺（FP THY）移植物中能高效发育，并重新填充T细胞和NK细胞耗竭且胸腺切除（ATX）小鼠的外周血。然而，这些小鼠中并未出现小鼠CD8⁺ T细胞对外周血的高效重新填充。因此，我们评估了胎猪胸腺和肝片段（FP THY LIV）移植物中小鼠CD8单阳性（SP）胸腺细胞的成熟和功能。通过TCR、I类MHC和Qa - 2表达上调以及热稳定抗原（HSA）在FP THY移植物中CD8 SP细胞上表达下调来衡量的表型成熟度，与正常对照小鼠宿主胸腺中的相似。FP THY移植物中胸腺细胞的细胞毒性T淋巴细胞（CTL）活性与正常小鼠宿主胸腺中的胸腺细胞相似，表明移植物中发生了CD8 SP细胞的功能成熟。此外，在FP THY移植物中观察到Vβ5.1/5.2⁺和Vβ11⁺ CD8 SP细胞的缺失效率与正常对照小鼠宿主胸腺中的相似。在FP THY移植物和正常对照宿主胸腺的CD8 SP细胞中也检测到表达Vβ6、Vβ7和Vβ8.1/8.2细胞的相似百分比。总之，我们的结果表明正常的阳性和阴性选择发生，并且小鼠CD8⁺细胞可以在FP THY移植物中经历正常的功能和表型成熟。因此，对于CD8⁺细胞无法重新填充ATX、T细胞耗竭、猪THY/LIV移植小鼠外周淋巴组织的原因，必须寻找其他解释。
