Differential roles of direct and indirect allorecognition pathways in the rejection of skin and corneal transplants.

Differential roles of direct and indirect allorecognition pathways in the rejection of skin and corneal transplants.
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DOI:
10.1097/tp.0b013e318191b38b
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发表时间:
2009-01-15
期刊:
影响因子:
6.2
通讯作者:
Benichou G
Benichou G
中科院分区:
医学2区
文献类型:
--
作者:
Boisgérault F;Liu Y;Anosova N;Dana R;Benichou G

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人们普遍认为,并不是所有的移植都会以同样的方式被排斥。然而,控制宿主对特定同种异体移植物的识别和排斥的外在和内在因素尚未得到很好的表征。我们比较了小鼠完全异体皮肤和角膜移植后激活的T细胞对供体抗原反应的机制。在角膜移植小鼠中,CD4+ T细胞反应完全由T细胞间接识别次要抗原并产生低水平的IL-2介导。相比之下,皮肤移植引发了直接和间接的CD4+ T细胞反应,主要针对MHC抗原,并以高IL-2水平为特征。虽然产生γIFN的CD8+ T细胞在皮肤和角膜移植小鼠中都被直接激活,但只有来自皮肤移植小鼠的CD8+ T细胞产生细胞毒性反应。接下来,我们研究了角膜移植诱导CD4+直接同种异体反应的失败是由于它们的免疫原性差还是由于放置部位(眼睛)。我们观察到皮下移植的角膜和眼内移植的脾细胞都能够直接诱导CD4+ T细胞的同种异体反应。这表明,角膜同种异体移植不能引起CD4+ T细胞的直接同种异体反应与两个因素的结合有关,它们的低免疫原性和眼睛的免疫特权特性。
It is generally accepted that all transplants are not rejected in the same fashion. However, the extrinsic and intrinsic factors that control the recognition and rejection of a particular allograft by the host are not well characterized. We compared the mechanisms underlying the response to donor antigens by T cells activated after transplantation of fully allogeneic skin and corneal grafts in mice. In corneal-transplanted mice, the CD4+ T cell response was exclusively mediated by T cells recognizing minor antigens in an indirect fashion and producing low levels of IL-2. In contrast, skin grafts elicited both direct and indirect CD4+ T cell responses primarily directed to MHC antigens and characterized by high IL-2 levels. While CD8+ T cells producing γIFN were activated directly in both skin- and corneal-grafted mice, only CD8+ T cells from skin-transplanted mice mounted a cytotoxic response. Next, we investigated whether failure of corneal transplants to induce a CD4+ direct alloresponse is due to their poor immunogenicity or to the site of placement (eye). We observed that corneas transplanted under the skin as well as splenocytes transplanted in the eye were both capable of inducing direct CD4+ T cell alloreactivity. This shows that, failure of orthotopic corneal allotransplants to elicit a CD4+ T cell direct alloresponse is associated with the combination of two factors, their low immunogenicity and the immune-privileged properties of the eye.
培养对大鼠中主要组织相容性复合物和不相容的甲状腺移植物生存的影响。
DOI: 10.1084/jem.157.1.348
发表时间: 1983-01-01
影响因子: 15.3
作者:
Bartlett, S T;Jennings, A S;Yu, C;Naji, A;Barker, C F;Silvers, W K
通讯作者: Silvers, W K