Theobald V A, Lauer J D, Kaplan F A, Baker K B, Rosenberg M
Organogenesis Inc., Cambridge, Massachusetts 02142.
Transplantation. 1993 Jan;55(1):128-33. doi: 10.1097/00007890-199301000-00024.
Cultured human dermal fibroblasts, smooth muscle cells, epidermal cells and endothelial cells were tested for immunogenicity in an in vitro allostimulation assay. Gamma interferon was used to induce MHC class II expression, since these cells constitutively express class I but not class II antigens. In contrast to human dermal fibroblasts, smooth muscle cells and epidermal cells, endothelial cells, were able to stimulate a significant proliferative response in normal allogeneic lymphocytes. Since ICAM-1 was also expressed on these cells, this inability to initiate allostimulation was probably not due to the absence of adhesion molecules. Addition of exogenous cytokines such as IL-1, IL-2, and TNF did not restore T cell proliferation in the test system. Therefore the inability of dermal fibroblasts, smooth muscle cells, and epidermal cells to initiate significant allostimulation was also not due to lack of cytokine production. It appears that certain cells lack as-yet-undefined costimulatory factors required for their effective recognition as foreign. These results support the notion that cultured human fibroblasts, smooth muscle cells, and epidermal cells could serve as building blocks of engineered "neutral allografts" for use across MHC barriers.
在体外异体刺激试验中,对培养的人真皮成纤维细胞、平滑肌细胞、表皮细胞和内皮细胞的免疫原性进行了检测。使用γ干扰素诱导MHC II类分子表达,因为这些细胞组成性表达I类但不表达II类抗原。与人类真皮成纤维细胞、平滑肌细胞和表皮细胞不同,内皮细胞能够在正常异体淋巴细胞中刺激显著的增殖反应。由于ICAM - 1也在这些细胞上表达,这种无法启动异体刺激的情况可能不是由于缺乏黏附分子。添加外源性细胞因子如IL - 1、IL - 2和TNF并不能恢复测试系统中的T细胞增殖。因此,真皮成纤维细胞、平滑肌细胞和表皮细胞无法启动显著的异体刺激也不是由于缺乏细胞因子产生。似乎某些细胞缺乏尚未明确的共刺激因子,这些因子是它们被有效识别为外来物所必需的。这些结果支持这样一种观点,即培养的人成纤维细胞、平滑肌细胞和表皮细胞可以作为构建跨越MHC屏障的工程化“中性同种异体移植物”的组成部分。