Ladiges W C, Storb R, Raff R F, Appelbaum F R, Sandmaier B, Schuening F, Graham T
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.
Bone Marrow Transplant. 1990 Jan;5(1):43-6.
Gene products of the major histocompatibility complex (MHC) have been shown to elicit lethal graft-versus-host disease (GVHD) in experimental animals. Antibodies specific for MHC cell surface determinants might therefore be expected to overcome histocompatibility barriers and influence survival of marrow graft recipients. GVHD can be consistently induced in dogs by transplanting donor marrow cells into lethally irradiated, unrelated, mismatched recipients. Three anti-Ia monoclonal antibodies were administered to five canine recipients, each at a dose of 0.2 mg/kg body weight per day intravenously for 10 days, beginning on day 0, the day of transplantation. Eight canine recipients were treated with antidog alloantiserum 10 ml/kg body weight per day intravenously on days -2 to day +20, in addition to receiving postgrafting methotrexate. The antiserum was generated by immunizing a matched littermate of the donor with peripheral blood cells of the recipient before transplantation. Survival was no different in the two groups of dogs, compared with historical controls without antibody treatment. A possible explanation for the failure of anti-MHC antibodies to modify acute GVHD in the dog is the inability of antibody to reach critical tissue sites targeted in GVHD.
主要组织相容性复合体（MHC）的基因产物已被证明在实验动物中可引发致死性移植物抗宿主病（GVHD）。因此，针对MHC细胞表面决定簇的特异性抗体有望克服组织相容性障碍并影响骨髓移植受者的存活。通过将供体骨髓细胞移植到经致死性照射、不相关且不匹配的受体中，可在犬类中持续诱导GVHD。从移植当天（第0天）开始，给5只犬类受体静脉注射三种抗Ia单克隆抗体，每天每千克体重0.2毫克，持续10天。除了移植后接受甲氨蝶呤治疗外，8只犬类受体在移植前第2天至移植后第20天每天静脉注射10毫升/千克体重的抗犬同种异体抗血清。该抗血清是通过在移植前用受体的外周血细胞免疫供体的同窝匹配动物产生的。与未接受抗体治疗的历史对照相比，两组犬类的存活率没有差异。抗MHC抗体未能改变犬类急性GVHD的一个可能解释是抗体无法到达GVHD靶向的关键组织部位。
