Lee R S, Grusby M J, Laufer T M, Colvin R, Glimcher L H, Auchincloss H
Tranplantation Unit, General Surgical Services, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
Transplantation. 1997 Apr 27;63(8):1123-33. doi: 10.1097/00007890-199704270-00012.
Skin grafts from mice that are deficient in the expression of both class I and class II major histocompatibility complex (MHC) antigens are rejected rapidly by normal recipients.
To determine the mechanism of this rejection, MHC-deficient skin grafts were placed on recipients with different degrees of antigenic disparity and on recipients depleted of selected T cell subpopulations. In addition, the recipient's T cells were examined in vitro for their responses before and after graft rejection.
The results indicate that (1) CD4+ cells provide help for this rejection by recognizing donor antigens presented by recipient class II antigens, and (2) CD8+ cells can participate as effector cells, recognizing residual class I antigens expressed by the MHC-deficient grafts.
The primary conclusion from these studies is that the supposedly MHC-deficient mice actually do have sufficient class I antigen expression to cause skin graft rejection. This finding prevents the use of these mice to answer definitively the question of whether grafts entirely lacking MHC antigens would be rejected. However, these studies do illustrate two important (although previously recognized) features of allogeneic skin graft rejection: (1) that rejection can be initiated by help provided entirely through the indirect pathway, and (2) that help provided through the indirect pathway is available for effector T cells sensitized directly by donor cells. However, the results from these and other studies suggest that indirect effector mechanisms would probably be able to destroy truly MHC-deficient grafts under some circumstances.
来自I类和II类主要组织相容性复合体(MHC)抗原表达均缺陷的小鼠的皮肤移植物会被正常受体迅速排斥。
为确定这种排斥反应的机制,将MHC缺陷的皮肤移植物移植到具有不同程度抗原差异的受体以及缺乏特定T细胞亚群的受体身上。此外,在体外检测受体T细胞在移植物排斥前后的反应。
结果表明:(1)CD4 +细胞通过识别由受体II类抗原呈递的供体抗原为这种排斥反应提供帮助;(2)CD8 +细胞可作为效应细胞参与其中,识别MHC缺陷移植物表达的残余I类抗原。
这些研究的主要结论是,所谓的MHC缺陷小鼠实际上确实具有足以导致皮肤移植物排斥的I类抗原表达。这一发现使得无法利用这些小鼠来明确回答完全缺乏MHC抗原的移植物是否会被排斥的问题。然而,这些研究确实阐明了同种异体皮肤移植物排斥的两个重要(尽管此前已被认识到)特征:(1)排斥反应可完全通过间接途径提供的帮助引发;(2)通过间接途径提供的帮助可用于由供体细胞直接致敏的效应T细胞。然而,这些研究及其他研究的结果表明,在某些情况下,间接效应机制可能能够破坏真正缺乏MHC的移植物。