Hultman C S, Cairns B A, deSerres S, Frelinger J A, Meyer A A
Department of Surgery, School of Medicine, University of North Carolina, Chapel Hill 27599-7210, USA.
Transplantation. 1995 Sep 27;60(6):584-9. doi: 10.1097/00007890-199509270-00011.
Cultured keratinocyte (CK) allografts have limited antigenicity and have been used as a skin replacement in patients with massive thermal injury. Recent data indicate that CK grafts are more immunogenic than previously believed and could compromise wound healing in the immunocompetent host. The purpose of this study was to determine if the immunosuppression of burn injury might affect the alloantigen response and minimize sensitization to CK allografts. CBA mice received a 0%, 20%, or 40% burn that was partially excised three days later and grafted with a full-thickness (FT) skin allograft, CK allograft, or CK autograft. Two weeks postburn, mice received FT tail skin allografts, which were observed for rejection. We observed that FT and CK allografts primed the unburned host with equal efficacy. However, burn injury selectively minimized priming by CK allografts, resulting in delayed rejection of second-set allografts. With evidence that burn injury inhibits host sensitization to CK allografts, we then examined the effect of burn size on CTL alloreactivity. Additional CBA mice underwent burn injury, excision, and grafting as described above. Host splenocytes were harvested two weeks later and tested on radiolabeled targets for allospecific cytotoxicity. CTLs from unburned mice primed with FT allografts demonstrated the greatest CTL lysis, followed next by CTLs from unburned mice covered with CK allografts. Burn injury inhibited CTL activity as a function of wound size. Activity of CTLs from burned mice primed with CK allografts improved after in vitro allostimulation but remained below that of CTLs from unburned, unprimed mice. We conclude that burn injury selectively inhibits the allospecific response to CK allografts. The decreased immunogenicity of CK allografts, when used for burn wound coverage, may improve the long-term survival of allogeneic keratinocytes, enhancing their potential as a biologic skin replacement.
培养的角质形成细胞（CK）同种异体移植物具有有限的抗原性，已被用作大面积热烧伤患者的皮肤替代物。最近的数据表明，CK移植物的免疫原性比以前认为的更强，可能会损害免疫功能正常宿主的伤口愈合。本研究的目的是确定烧伤损伤的免疫抑制是否会影响同种异体抗原反应，并使对CK同种异体移植物的致敏作用最小化。CBA小鼠接受0%、20%或40%的烧伤，三天后部分切除烧伤部位，然后移植全层（FT）皮肤同种异体移植物、CK同种异体移植物或CK自体移植物。烧伤后两周，小鼠接受FT尾部皮肤同种异体移植物，并观察其排斥反应。我们观察到，FT和CK同种异体移植物以相同的效力使未烧伤的宿主致敏。然而，烧伤损伤选择性地使CK同种异体移植物的致敏作用最小化，导致二次同种异体移植物的排斥反应延迟。有证据表明烧伤损伤会抑制宿主对CK同种异体移植物的致敏作用，我们随后研究了烧伤面积对CTL同种异体反应性的影响。另外的CBA小鼠如上所述进行烧伤损伤、切除和移植。两周后收集宿主脾细胞，并在放射性标记的靶细胞上测试其同种特异性细胞毒性。用FT同种异体移植物致敏的未烧伤小鼠的CTL表现出最大的CTL裂解作用，其次是覆盖有CK同种异体移植物的未烧伤小鼠的CTL。烧伤损伤抑制CTL活性，且与伤口大小有关。用CK同种异体移植物致敏的烧伤小鼠的CTL活性在体外同种异体刺激后有所改善，但仍低于未烧伤、未致敏小鼠的CTL活性。我们得出结论，烧伤损伤选择性地抑制对CK同种异体移植物的同种特异性反应。当用于烧伤创面覆盖时，CK同种异体移植物免疫原性的降低可能会提高同种异体角质形成细胞的长期存活率，增强其作为生物皮肤替代物的潜力。
