Adoptively transferred CD4+ lymphocytes from CD8 -/- mice are sufficient to mediate the rejection of MHC class II or class I disparate skin grafts.
Adoptively transferred CD4+ lymphocytes from CD8 -/- mice are sufficient to mediate the rejection of MHC class II or class I disparate skin grafts.
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从 CD8 -/- 小鼠过继转移的 CD4 淋巴细胞足以介导 MHC II 类或 I 类不同皮肤移植物的排斥反应。
DOI：
10.4049/jimmunol.156.11.4114
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发表时间：
1996
影响因子：
4.4
通讯作者：
W. Fung
中科院分区：
文献类型：
--
作者：
A. Dalloul;E. Chmouzis;Karen Ngo;W. Fung
最近的研究表明，CD 4+细胞通过直接识别同种异体MHC Ⅱ类抗原和间接识别自身抗原提呈细胞加工的MHC肽段来启动同种异体移植排斥反应。这两种途径都被证明有助于CD 8+细胞最终裂解同种异体MHC I类呈递靶点。然而，几乎没有证据表明CD 4+细胞足以引起移植物排斥反应。我们研究了CD 8缺陷（CD 8-/-）小鼠的皮肤移植排斥反应。我们发现BALB/cJ（H-2d）CD 8-/-小鼠可以排斥来自MHC I类或MHC II类Ags缺陷的C57 BL/6 J（H-2b）小鼠的同种异体皮肤。为了了解CD 4+细胞在这一过程中的作用，我们将它们从CD 8-/-小鼠中分离出来，并将它们转移到BALB/cJ裸鼠中，这些裸鼠已经移植了来自MHC I类或MHC II类缺陷动物的同种异体皮肤（H-2b）。注射CD 4+细胞的裸鼠排斥MHC II类分子，尽管速度较慢，但排斥MHC I类分子不同的皮肤。我们在体外证明了CD 4+细胞对MHC I类或MHC II类不同的靶点没有细胞毒性，并且它们通过间接识别来识别MHC I类同种异体靶点。同种异体细胞刺激后，CD 4+细胞产生Th 1细胞因子，但不产生IL-4。此外，与未重建的小鼠相比，移植到用CD 4+细胞重建的裸鼠皮肤上的移植物内TNF-α升高。这表明单独的MHC II类或MHC I类引导的CD 4+细胞足以通过产生精氨酸诱导的损伤来诱导排斥。
Recent studies revealed that CD4+ cells initiate allograft rejection through direct recognition of allogeneic MHC class II Ags and indirect recognition of MHC peptides processed by self APCs. Both pathways were shown to help CD8+ cells that eventually lysed allogeneic MHC class I-presenting targets. There was little evidence, however, that CD4+ cells are sufficient for graft rejection. We studied skin graft rejection by CD8-deficient (CD8 -/-) mice. We showed that BALB/cJ(H-2d) CD8 -/- mice could reject allogeneic skin from C57BL/6J(H-2b) mice deficient in MHC class I or in MHC class II Ags. To understand the role of CD4+ cells in this process, we isolated them from CD8 -/- mice and transferred them to BALB/cJ nude mice that had been grafted with allogeneic skin (H-2b) from animals deficient in MHC class I or MHC class II. Nude mice injected with CD4+ cells rejected MHC class II and, albeit more slowly, MHC class I disparate skins. We showed in vitro evidence that CD4+ cells were not cytotoxic toward MHC class I or MHC class II disparate targets and that they recognized MHC class I allogeneic targets through indirect recognition. CD4+ cells produced Th1 cytokines, but not IL-4, following stimulation with allogeneic cells. Furthermore, intragraft TNF-alpha was elevated in skin grafted onto nude mice reconstituted with CD4+ cells compared with nonreconstituted mice. This suggests that MHC class II- or MHC class I-guided CD4+ cells alone are sufficient to induce rejection by the generation of cytokine-induced lesions.