Mouse-heart grafts expressing an incompatible carbohydrate antigen. II. Transition from accommodation to tolerance.
Mouse-heart grafts expressing an incompatible carbohydrate antigen. II. Transition from accommodation to tolerance.
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表达不相容的碳水化合物抗原的小鼠心脏移植物。
DOI：
10.1097/01.tp.0000109276.57772.6d
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Galili,Uri
中科院分区：
文献类型：
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作者：
Ogawa,Haruko;Mohiuddin,MuhammadM;Yin,Deng-Ping;Shen,Jikun;Chong,AnitaS;Galili,Uri
背景。同种异体移植物对不相容ABO抗原的免疫反应可能导致排斥、调节或免疫耐受。我们的目的是建立一个模型来研究α 1,3半乳糖转移酶敲除（KO）小鼠对不相容碳水化合物抗原的这三种类型的免疫反应。KO小鼠缺乏α-gal表位，用表达α-gal表位的猪肾膜（PKM）免疫后可产生抗gal抗体。方法：用表达α-gal表位的同基因野生型（WT）心脏移植KO小鼠。随后，对小鼠进行致死照射，并接受来自PKM免疫的KO小鼠的淋巴细胞，包括记忆抗gal B细胞。通过移植心功能和PKM免疫后anti-Gal的产生来测定移植物对不相容α-gal表位的免疫反应。抗半乳糖B细胞暴露于WT心脏α-半乳糖表位1 - 2周后分化为产生非细胞溶解性调节抗体的细胞。暴露较长时间（2-4周）诱导从适应到耐受的转变，表明小鼠无法产生抗gal抗体，尽管多次PKM免疫。结论：在没有t细胞帮助的情况下，暴露于移植器官不相容的碳水化合物抗原的抗碳水化合物B细胞首先分化为能够产生调节抗体的细胞，但在长时间暴露后，这些B细胞逐渐产生耐受性。这些发现表明，在abo血型不相容的同种异体移植物受体中，长期的t细胞抑制可能导致对不相容血型抗原的类似耐受诱导。
Background.Immune response to incompatible ABO antigens on allografts may result in rejection, accommodation, or immune tolerance. Our objective has been to develop a model for studying these three types of immune response to incompatible carbohydrate antigen in α1, 3galactosyltransferase knockout (KO) mice. KO mice lack the α-gal epitope and can produce the anti-Gal antibody against it after immunization with pig kidney membranes (PKM) that express this epitope.Methods.KO mice were transplanted with syngeneic wild-type (WT) heart expressing α-gal epitopes. Subsequently, the mice were lethally irradiated and received lymphocytes including memory anti-Gal B cells from PKM immunized KO mice. Immune response to incompatible α-gal epitopes on the graft was determined by transplanted-heart function and by production of anti-Gal after PKM immunizations.Results.Anti-Gal B cells exposed for 1 to 2 weeks to α-gal epitopes of WT hearts differentiate into cells producing noncytolytic accommodating antibodies. Exposure for longer periods (2–4 weeks) induces a transition from accommodation into tolerance, indicated by the inability of mice to produce anti-Gal antibodies despite repeated PKM immunizations. WT hearts in accommodating and in tolerized mice continue to function for months.Conclusions.In the absence of T-cell help, anticarbohydrate B cells exposed to incompatible carbohydrate antigens of transplanted organs differentiate first into cells capable of producing accommodating antibodies, but, after prolonged exposure, these B cells gradually become tolerized. These findings suggest that prolonged T-cell suppression in recipients of ABO-incompatible allografts may result in a similar induction of tolerance to incompatible blood-group antigens.