Neonatally tolerant rats actively eliminate donor‐specific lymphocytes despite persistent chimerism
Neonatally tolerant rats actively eliminate donor‐specific lymphocytes despite persistent chimerism
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尽管存在持续的嵌合现象，新生耐受大鼠仍主动消除供体特异性淋巴细胞
DOI：
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发表时间：
1996
影响因子：
5.4
通讯作者：
E. Bell
中科院分区：
文献类型：
--
作者：
A. Cutler;E. Bell
在出生时，将来自同种异型标记的PVG-RT 7 b和PVG-RT 1u-RT 7 b品系的大鼠注射来自无胸腺裸大鼠的半同种异体F1骨髓（BM）细胞（PVG-rnu/rnu x PVG-RT 1u-rnu/rnu），以诱导新生儿耐受。作为成年动物，97%的动物接受供体特异性同种异体皮肤移植，大多数（65%）大鼠是嵌合体，表达供体品系的主要组织相容性复合体I类和同种异型标记物。当PVG-RT 1u-RT 7 b大鼠在出生时注射完全同种异体PVG-rnu/rnu裸BM细胞时，获得了类似的结果：成年后，94%接受了供体特异性皮肤同种异体移植物，76%的受体是嵌合体。在F1 BM细胞耐受的大鼠外周血中，发现供体来源的CD 4 T细胞、CD 8 T细胞和B细胞数量较低（< 2%）。很大一部分T细胞具有最近胸腺移民的表型，表明它们是新产生的。所有的证据都与克隆缺失耐受一致，在胸腺内集中诱导。胸腺是嵌合的，胸腺细胞在体外对供体特异性单倍型的同种异体抗原没有反应;供体特异性皮肤同种异体移植物在用来自耐受动物的CD 4 + CD 8 −胸腺细胞或外周CD 4 T细胞重建的无胸腺裸受体上无限期存活。嵌合状态是有趣的，因为PVG和PVG-RT 1u大鼠品系含有自然杀伤（NK）细胞系统，可以快速消除（24小时内）静脉注射的同种异体或半同种异体淋巴细胞-这种现象称为同种异体淋巴细胞毒性或ALC。当测试新生耐受大鼠时，ALC指数（细胞杀伤的量度）在非嵌合耐受大鼠中不变，并且显著改变（减少杀伤），但在嵌合动物中没有消除。因此，在T细胞群体中诱导特异性耐受的同种异体BM细胞的注射未能耐受NK细胞系统，从而允许持续杀死新产生的供体来源的淋巴细胞并使同种异体BM细胞的存活处于危险之中。这对临床移植有着有趣的意义。
Rats from the allotype‐marked PVG‐RT7b and PVG‐RT1u‐RT7b strains were injected at birth with semi‐allogeneic F1 bone marrow (BM) cells from athymic nude rats (PVG‐rnu/rnu x PVG‐RT1u‐rnu/rnu) to induce neonatal tolerance. As adults, 97% of the animals accepted donor‐specific allogeneic skin grafts and a majority (65%) of rats were chimeric, expressing the major histocompatibility complex class I and allotype marker of the donor strain. Similar results were obtained when PVG‐RT1u‐RT7b rats were injected at birth with fully allogeneic PVG‐rnu/rnu nude BM cells: as adults, 94% accepted donor‐specific skin allografts and 76% of recipients were chimeric. Donor‐derived CD4T cells, CD8T cells and B cells were found in low numbers (< 2%) in peripheral blood of rats made tolerant by F1 BM cells. A large proportion of T cells bore the phenotype of recent thymic emigrants, suggesting that they were newly produced. All the evidence was consistent with clonal deletion tolerance, induced centrally within the thymus. The thymus was chimeric and thymocytes failed to respond in vitro to alloantigens of the donor‐specific haplotype; donor‐specific skin allografts survived indefinitely on athymic nude recipients reconstituted with CD4+CD8− thymocytes or peripheral CD4T cells from tolerant animals. The chimeric state was interesting, since the PVG and PVG‐RT1u rat strains contain a natural killer (NK) cell system that rapidly eliminates (within 24 h) intravenously injected allogeneic or semi‐allogeneic lymphocytes – a phenomenon known as allogeneic lymphocyte cytotoxicity or ALC. When neonatal tolerant rats were tested, the ALC index (a measure of cell killing) was unchanged in nonchimeric tolerant rats and significantly altered (reduced killing), but not abolished in chimeric animals. Hence, the injection of allogeneic BM cells which induced specific tolerance in the T cell population failed to tolerize the NK cell system, allowing the constant killing of newly produced donor‐derived lymphocytes and putting at risk the very survival of the allogeneic BM cells. This has interesting implications for clinical transplantation.
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新生儿对 H-2 同种异体抗原的耐受性。
影响因子：
6.2
作者：
Streilein,JW
通讯作者：
Streilein,JW
大鼠体内 RT7 和 LCA 抗原的单克隆抗体：细胞分布和分离分析。
影响因子：
--
作者：
Mojcik,CF;Greiner,DL;Goldschneider,I;Lubaroff,DM
通讯作者：
Lubaroff,DM
大鼠的自然细胞毒性：品系分布和遗传学。
影响因子：
4.3
作者：
McNeilage,LJ;Heslop,BF;Heyworth,MR;Gutman,GA
通讯作者：
Gutman,GA
对新生儿移植耐受具有抗性的小鼠胸腺中供体嵌合、同种异体反应性宿主 T 细胞和记忆细胞发育的表征。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ruiz,P;Nassiri,M;Viciana,AL;Padmanabhan,J;Streilein,JW
通讯作者：
Streilein,JW
体外测定未能准确预测新生儿诱导的 H-2 耐受性的存在。
影响因子：
6.2
作者：
Streilein,JW;Strome,P;Wood,PJ
通讯作者：
Wood,PJ