Wise M, Zelenika D, Bemelman F, Latinne D, Bazin H, Cobbold S, Waldmann H
Sir William Dunn School of Pathology, Oxford, GB.
Eur J Immunol. 1999 Jan;29(1):156-67. doi: 10.1002/(SICI)1521-4141(199901)29:01<156::AID-IMMU156>3.0.CO;2-K.
We have re-investigated the roles of CD4 and CD8 T cell subsets in skin graft rejection across a single class I MHC disparity. Recipient mice were transplanted with skin from donors transgenic for the class I MHC molecule Kb. As expected, CD8 T cells were sufficient for rapid injection; but surprisingly, CD4 T cells were also competent to do the same. Rejection was dependent on one or the other subset, since elimination of both resulted in indefinite graft survival. The possibility that alloantibody was the downstream effector of CD4 mediated rejection was excluded because CD8-depleted mice rendered B cell deficient still rejected rapidly, but T cell-depleted recipients with pre-existing high titers of alloantibody were unable to do so. In addition, if CD4 cells act to reject by recruiting and/or activating macrophages then this was not dependent on CR3, IFN-gamma or TNF-alpha. Transplantation of skin grafts where the MHC class I disparity was at the level of passenger leukocytes only, demonstrated that transient bystander damage could occur, but that this was insufficient to result in full rejection. We surmise that for CD4 T cells to reject an MHC class I-incompatible graft it is necessary that an appropriate allogeneic peptide is processed and presented in the context of recipient MHC class II. CD4 T cells from B6 mice may fail to reject skin from MHC class I mutants because of the lack of such MHC class II-restricted presentation.
我们重新研究了CD4和CD8 T细胞亚群在单一I类主要组织相容性复合体（MHC）差异的皮肤移植排斥反应中的作用。将来自I类MHC分子Kb转基因供体的皮肤移植到受体小鼠体内。正如预期的那样，CD8 T细胞足以引发快速排斥；但令人惊讶的是，CD4 T细胞也有同样的能力。排斥反应依赖于其中一个亚群，因为消除这两个亚群都会导致移植皮肤长期存活。由于去除CD8的小鼠即使B细胞缺陷仍能快速排斥，而预先存在高滴度同种抗体的T细胞缺陷受体则无法排斥，因此排除了同种抗体是CD4介导的排斥反应下游效应器的可能性。此外，如果CD4细胞通过招募和/或激活巨噬细胞来发挥排斥作用，那么这并不依赖于补体受体3（CR3）、γ干扰素（IFN-γ）或肿瘤坏死因子-α（TNF-α）。仅在过客白细胞水平存在I类MHC差异的皮肤移植实验表明，可能会发生短暂的旁观者损伤，但这不足以导致完全排斥。我们推测，CD4 T细胞要排斥I类MHC不相容的移植皮肤，必须有合适的同种异体肽在受体II类MHC的背景下进行加工和呈递。来自B6小鼠的CD4 T细胞可能无法排斥I类MHC突变体的皮肤，因为缺乏这种II类MHC限制性呈递。
