Ildstad S T, Wren S M, Bluestone J A, Barbieri S A, Stephany D, Sachs D H
J Immunol. 1986 Jan;136(1):28-33.
Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts, whether or not the allogeneic bone marrow was T cell depleted. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. In addition, experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it. This system may be helpful as a model for the study of alloresistance and for the identification of syngeneic cell phenotypes, which when present prevent engraftment of allogeneic marrow.
用T细胞去除的同基因加T细胞去除的异基因骨髓混合物（B10 + B10.D2----B10）重建受致死性照射的小鼠，可导致混合淋巴细胞嵌合体的诱导、良好的存活率、对随后供体品系皮肤移植的特异性体内移植耐受性，以及通过混合淋巴细胞反应（MLR）增殖和细胞介导的淋巴细胞溶解（CML）细胞毒性试验评估的对异基因供体淋巴样成分的特异性体外无反应性。当B10受体小鼠接受混合骨髓接种物，其中同基因成分未进行T细胞去除时，无论异基因供体骨髓是否经过处理，它们都完全由宿主型细胞重新填充，迅速排斥供体型皮肤同种异体移植物，并且通过CML和MLR试验在体外对异基因供体有反应。相反，混合骨髓接种物的同基因成分进行T细胞去除导致对异基因供体品系皮肤移植的特异性接受，无论异基因骨髓是否进行T细胞去除。此类动物在体外通过CML和MLR对异基因供体淋巴样成分无特异性反应，但对第三方有反应。当同基因和异基因骨髓都进行T细胞去除时，在混合重建的宿主体内检测到不同比例的宿主型和供体型淋巴样成分。当仅同基因骨髓进行T细胞去除时，动物完全由供体型细胞重新填充。尽管这些动物通过CML和MLR在体外具有可检测到的抗宿主（B10）反应性，并重建为完全异基因嵌合体，但它们表现出良好的存活率，且体内无移植物抗宿主病的证据。此外，在最后一组实验中，将未处理的供体脾细胞添加到接种物中的实验表明，T细胞去除的同基因骨髓细胞的存在可减少移植物抗宿主病及其死亡率。该系统可能有助于作为研究同种异体抗性和鉴定同基因细胞表型的模型，当同基因细胞表型存在时可阻止异基因骨髓的植入。
