Active clonal deletion in neonatal H-2 tolerance.
Active clonal deletion in neonatal H-2 tolerance.
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新生儿 H-2 耐受性中的主动克隆缺失。
DOI：
10.1111/j.1749-6632.1982.tb36113.x
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发表时间：
1982
影响因子：
5.2
通讯作者：
Strome,P
中科院分区：
文献类型：
--
作者：
Streilein,JW;Gruchalla,RS;Wood,P;Strome,P
通过将异基因造血细胞接种到新生小鼠中诱导的移植耐受首次实现于大约30年前。有了这一独特的成就，实验验证了克隆选择假说所阐述的F。M. B~ rnet.~在接下来的几十年里，关于自我/非自我辨别机制的概念范式开始主导免疫学思想。虽然后来出现了许多其他模型的免疫耐受性和特定的无反应性，学科继续返回到经典模型作为标准，当代思想的判断。目前，世界各地的许多实验室都在从事新生儿移植耐受性实验的复兴，并出现了一组令人兴奋的新观察结果4我们已经加入了这一追求，但我们的方法的范围限制在免疫遗传学的考虑。也就是说，通过采用各种各样的遗传定义的H-2重组和同源小鼠品系，我们已经探讨了免疫遗传学基础的耐受性产生的半同种异体脾和骨髓细胞静脉注射给新生儿收件人。通过选择在H-2复合体的一个或多个区域不同的菌株组合，我们希望比较和对比由此获得的耐受性的类型和程度。我们最初的实验通过揭示以下重要发现证实了这种方法的有效性。(1)虽然新生小鼠对H-2基因编码的任何和所有同种抗原均可诱导移植耐受，但并非所有决定簇都具有同等的致耐受性。I1类主要组织相容性（MHC）抗原（Ia）非常容易诱导特异性耐受，而I类决定簇则要困难得多。（2）如果赋予耐受性的接种物表达两种类型决定簇的差异，则I1类抗原具有改善I类抗原的致耐受性潜力的进一步性质。这种效应的遗传图谱已经定位于H-2的ZJIE亚区，该染色体片段的一部分被怀疑在其他控制免疫抑制的系统中。6（3）长期H-2耐受的成年小鼠能够以看似不适当的方式排斥第三方皮肤同种异体移植物，该皮肤同种异体移植物表达由宿主和赋予耐受性的接种物的供体的聚集遗传信息所包含的独特的H-2决定簇阵列。这些结果暗示了接枝物上的Z区分子限制和引导
Transplantation tolerance induced by the inoculation of allogeneic hematopoietic cells into neonatal mice was first achieved approximately thirty years ago.', With this singular achievement, experimental verification was claimed for the clonal selection hypothesis as formulated by F. M. B~ rnet.~ Over the next several decades, a conceptual paradigm concerning the mechanism of self/non-self discrimination came to dominate immunological thinking. While numerous other models of immunological tolerance and specific unresponsiveness have emerged subsequently, the discipline continues to return to the classical model as the standard by which contemporary ideas are judged. At present, numerous laboratories around the world are engaged in a renaissance of experimentation with neonatal transplantation tolerance and an exciting new set of observations has emergeda4 We have joined this pursuit, but have restricted the scope of our approaches to immunogenetic considerations. That is, by employing a wide assortment of genetically defined H-2 recombinant and congenic mouse strains, we have explored the immunogenetic basis of tolerance produced by administering semiallogeneic spleen and bone marrow cells intravenously to neonatal recipients. By selecting strain combinations disparate at one or more regions of the H-2 complex, we hoped to compare and contrast the type and degree of tolerance thus achieved. Our initial experiments confirmed the validity of this approach by revealing the following important findings.(1) While transplantation tolerance can be induced in neonatal mice to any and all alloantigens encoded by H-2 genes, not all determinants are equally tolerogenic. Class I1 major histocompatibility (MHC) antigens (Ia) inducc specific tolerance with great facility; class I determinants do so with considerably more difficulty. 5 (2) Class I1 antigens have the further property of improving the tolerogenic potential of class I antigens if the tolerance-conferring inoculum expresses disparities of both types of determinants. Genetic mapping of this effect has been localized to the ZJIE subregions of H-2, a portion of this chromosomal segment that has been suspected in other systems of governing immune suppression. 6 (3) Long-term H-2-tolerant adult mice are capable of rejecting, in a seemingly inappropriate fashion, third party skin allografts expressing a unique array of H-2 determinants subsumed by the aggregate genetic information of the host and the donor of the tolerance-conferring inoculum. These results hint at the possibility that Z region molecules on the graft restrict and direct