Chitilian H V, Auchincloss H
Transplantation Unit, Massachusetts General Hospital, Boston 02114, USA.
J Heart Lung Transplant. 1997 Feb;16(2):153-9.
Mice deficient in the expression of either class I or class II major histocompatibility complex (MHC) antigens have been generated by use of the technique of gene disruption by homologous recombination. These animals have subsequently been mated to generate mice that are deficient in the expression of both classes of MHC antigens. Class I MHC-deficient animals have a greater than 90% reduction in cell surface expression of MHC I molecules; however, they do express low levels of class I heavy chains on their cells. Furthermore, class I-deficient mice have very few CD8S+R T cells. Class II MHC-deficient animals have no detectable expression of class II MHC molecules and a reduction in the CD4+ T cell population. Mice deficient in both MHC antigens share the characteristics of the two founder animals: low levels of class I heavy chain expression, no detectable class II expression and reduced levels of CD4+ and CD8+ T cells. Allotransplantation experiments with these animals have suggested that different mechanisms of graft rejection predominate depending on the target organ and have provided evidence for the role of the indirect pathway of antigen recognition in graft rejection. Xenotransplantation experiments involving these animals have revealed that donor MHC deficiency offers no protection to the graft, suggesting that strategies to eliminate MHC antigen expression will not be successful in generating "universal donors."
利用同源重组基因破坏技术已培育出缺乏I类或II类主要组织相容性复合体（MHC）抗原表达的小鼠。随后将这些动物进行交配，以培育出缺乏两类MHC抗原表达的小鼠。I类MHC缺陷动物细胞表面MHC I分子的表达减少90%以上；然而，它们的细胞确实表达低水平的I类重链。此外，I类缺陷小鼠的CD8+ T细胞很少。II类MHC缺陷动物没有可检测到的II类MHC分子表达，CD4+ T细胞数量减少。两种MHC抗原均缺陷的小鼠具有两种亲本动物的特征：I类重链表达水平低，没有可检测到的II类表达，以及CD4+和CD8+ T细胞水平降低。对这些动物进行的同种异体移植实验表明，根据靶器官不同移植排斥的主导机制不同，并为抗原识别间接途径在移植排斥中的作用提供了证据。涉及这些动物的异种移植实验表明，供体MHC缺陷对移植物没有保护作用，这表明消除MHC抗原表达的策略在培育“通用供体”方面不会成功。
