Blazar B R, Taylor P A, Boyer M W, Panoskaltsis-Mortari A, Allison J P, Vallera D A
Department of Pediatrics, University of Minnesota Hospital and Clinic, Minneapolis 55455, USA.
J Immunol. 1997 Oct 1;159(7):3460-73.
Graft-vs-leukemia (GVL) can reduce relapse rates after bone marrow transplantation (BMT). Delayed lymphocyte infusion (DLI) post-BMT can mediate a potent GVL effect with less graft-vs-host disease (GVHD) than would be observed if given early post-BMT. In vivo CD28/B7 blockade can reduce GVHD lethality, and B7 ligand expression can augment an antitumor immune response in mice. To examine the role of CD28/B7 interactions in DLI-mediated GVL, we established murine allogeneic BMT models in C57BL/6 (B6) recipients of C1498 (B6 acute myeloid leukemia) or EL4 (B6 acute T cell leukemia) that closely mimic human GVL. Recipients of C1498 and DLI had a marked reduction in relapse. GVL was blocked by anti-B7 mAb infusion. In contrast, recipients of EL4 cells and B10.BR DLI had a more modest GVL effect. The forced expression of B7-1 on EL4 cells markedly augmented the GVL effect of DLI, in contrast to the forced expression of B7-2 on EL4 cells. Relapse rates observed in recipients of C1498-B7-1 and DLI were significantly lower than in recipients of parental C1498 cells. We conclude that the administration of anti-B7 mAbs may impair the GVL effect of DLI and that the forced expression of B7-1 ligands stimulates a GVL effect without adversely affecting the GVHD lethality effect of DLI.
移植物抗白血病（GVL）作用可降低骨髓移植（BMT）后的复发率。BMT后延迟淋巴细胞输注（DLI）可介导强大的GVL效应，与BMT后早期输注相比，其移植物抗宿主病（GVHD）较少。体内CD28/B7阻断可降低GVHD致死率，并且B7配体表达可增强小鼠的抗肿瘤免疫反应。为了研究CD28/B7相互作用在DLI介导的GVL中的作用，我们在C57BL/6（B6）受体小鼠中建立了同种异体BMT模型，受体小鼠接受C1498（B6急性髓性白血病）或EL4（B6急性T细胞白血病）移植，该模型能紧密模拟人类GVL。接受C1498和DLI的受体复发率显著降低。输注抗B7单克隆抗体可阻断GVL。相比之下，接受EL4细胞和B10.BR DLI的受体GVL效应较适度。与在EL4细胞上强制表达B7-2相比，在EL4细胞上强制表达B7-1可显著增强DLI的GVL效应。接受C1498-B7-1和DLI的受体的复发率显著低于接受亲本C1498细胞的受体。我们得出结论，给予抗B7单克隆抗体可能会损害DLI的GVL效应，并且强制表达B7-1配体可刺激GVL效应，而不会对DLI的GVHD致死效应产生不利影响。
