Hardy M A, Lau H, Weber C, Reemtsma K
Ann Surg. 1984 Oct;200(4):441-50. doi: 10.1097/00000658-198410000-00005.
The effect of ultraviolet (UV) irradiation on the immunogenicity of rat pancreatic islets was examined in allograft and xenograft models. Direct UV irradiation (900 J/m2) of Lewis islets, isolated and hand-picked, does not alter pancreatic islet endocrine function in isograft experiments and results in indefinite islet allograft survival in streptozocin diabetic ACI rats without chronic immunosuppression. Direct UV irradiation, at an appropriate dose, also leads to indefinite islet xenograft survival of Lewis islets in B10-BR diabetic mice and prolonged survival of rat islets in Balb/C mice. When direct UV irradiation of islet allografts did not result in indefinite islet allograft prolongation [Wistar/Furth (W/F) to diabetic Lewis], the addition of brief peritransplant immunosuppression with cyclosporine (days 0, +1, and +2) resulted in permanent acceptance of islet allografts, a result not achieved by cyclosporine alone. The effectiveness of UV irradiation in abrogating islet allograft rejection in several experimental models is supported by in vitro studies showing that UV irradiation of stimulator cells, peripheral blood lymphocytes, splenocytes, and isolated rat dendritic cells abolishes any significant stimulation by such cells of totally histoincompatible thoracic duct responder lymphocytes. In vitro nonreactivity of mixed lymphocyte culture (MLC) with UV-irradiated stimulator cells and in vivo permanent allograft acceptance are reversed by the addition of a small number of untreated donor-type dendritic cells to either the MLC or the recipient bearing the permanent graft. The authors suggest that the primary effect of UV irradiation on immune alteration of islet allografts and xenografts is due to induction of a major metabolic change in the dendritic cells in the graft. This then leads to defective antigen presentation and results in either permanent or prolonged allograft and xenograft acceptance, depending on the degree of MLC stimulation between the islet donor and the diabetic recipient.
在同种异体移植和异种移植模型中，研究了紫外线（UV）照射对大鼠胰岛免疫原性的影响。在同基因移植实验中，对分离并挑选出的Lewis胰岛进行直接紫外线照射（900 J/m²），不会改变胰岛内分泌功能，并且在无慢性免疫抑制的链脲佐菌素诱导的糖尿病ACI大鼠中可使胰岛同种异体移植长期存活。适当剂量的直接紫外线照射，还可使Lewis胰岛在B10 - BR糖尿病小鼠中异种移植长期存活，并使大鼠胰岛在Balb/C小鼠中存活时间延长。当胰岛同种异体移植的直接紫外线照射未导致胰岛同种异体移植长期存活延长时[Wistar/Furth（W/F）对糖尿病Lewis]，移植时短期使用环孢素进行免疫抑制（第0天、+1天和+2天）可使胰岛同种异体移植被永久接受，单独使用环孢素无法达到此效果。体外研究表明，紫外线照射刺激细胞、外周血淋巴细胞、脾细胞和分离的大鼠树突状细胞后，这些细胞对完全组织不相容的胸导管反应性淋巴细胞的任何显著刺激均被消除，这支持了紫外线照射在多个实验模型中消除胰岛同种异体移植排斥反应的有效性。添加少量未处理的供体型树突状细胞至混合淋巴细胞培养（MLC）或接受永久移植的受体中，可逆转紫外线照射刺激细胞的混合淋巴细胞培养（MLC）体外无反应性和体内移植永久接受的情况。作者认为，紫外线照射对胰岛同种异体移植和异种移植免疫改变的主要作用是诱导移植中树突状细胞发生主要代谢变化。这进而导致抗原呈递缺陷，并根据胰岛供体与糖尿病受体之间MLC刺激的程度，导致同种异体移植和异种移植被永久或长期接受。
