Levinson R, Gillis M, Goldberg E H, Osler T
Department of Microbiology, University of New Mexico, Albuquerque 87131.
J Burn Care Rehabil. 1988 Nov-Dec;9(6):623-8. doi: 10.1097/00004630-198811000-00011.
Treatment of large burns would be simplified by the development of a nonsensitizing allograft which would survive permanently. In our hands, in vitro immune modification of the allograft has prolonged graft survival in mice across major histocompatibility barriers (H-2d to H-2b) by 36% (steroid pretreatment) and 25% (monoclonal antibody to the Iad antigen found on donor Langerhans cells). To our knowledge, monoclonal antibody has not been employed in this capacity previously. Double grafting studies suggest that neither MK-D6 nor steroids enhance graft survival by systemic immunosuppression. Moreover, MK-D6 acts upon the afferent limb of the immune response while steroids interrupt the efferent limb (and probably afferent limb). These effects are not additive. This modest improvement in allograft survival may have profound importance since allografts supported briefly by host immunosuppression have gone on to indefinite survival in burn victims without further immunologic intervention. This improvement in allograft survival is of fundamental immunologic interest. If synergistic pretreatments can be found, it may ultimately allow allografting of burn victims with the expectation of indefinite graft survival.
开发一种能永久存活的无致敏性同种异体移植物将简化大面积烧伤的治疗。在我们的研究中,对同种异体移植物进行体外免疫修饰,使小鼠跨主要组织相容性屏障(从H-2d到H-2b)的移植物存活时间延长了36%(类固醇预处理)和25%(针对供体朗格汉斯细胞上发现的Iad抗原的单克隆抗体)。据我们所知,单克隆抗体此前尚未用于此目的。双重移植研究表明,MK-D6和类固醇均不是通过全身免疫抑制来提高移植物存活率。此外,MK-D6作用于免疫反应的传入支,而类固醇则阻断传出支(可能还有传入支)。这些作用并非相加的。同种异体移植物存活的这种适度改善可能具有深远意义,因为在宿主免疫抑制短暂支持下的同种异体移植物在烧伤患者中已能在无进一步免疫干预的情况下实现无限期存活。同种异体移植物存活的这种改善具有根本的免疫学意义。如果能找到协同预处理方法,最终可能使烧伤患者进行同种异体移植并期望移植物无限期存活。