Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2007
Prolongation of corneal allograft survival by CTLA4-FasL in a murine model.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shi Weiyun, Chen Min, Xie Lixin
Аннотация
BACKGROUND: To investigate the therapeutic effect of CTLA4-FasL-B7 costimulatory pathway blockage-on graft survival in a murine model of corneal transplantation.
METHODS: Orthotopic penetrating keratoplasty was performed on BALB/c mice. The mice were randomized into four groups: the isograft group, untreated allograft group, cyclosporine A drug delivery system (CsA DDS)-anterior chamber implanted group, and 10 microg/mL CTLA4-FasL-treated group. Allografts were from C57BL/6 mice. Survival time of corneal grafts was evaluated. Immunohistological method and TdT-mediated dUTP Nick End Labeling (TUNEL) were applied for the detection of CD4+ T cells and apoptotic cells in corneal transplants. To assess whether peripheral immune tolerance appeared after the treatment of CTLA4-FasL, CsA DDS-implanted- and CTLA4-FasL-treated BALB/c mice with clear grafts received skin allografts at 4 weeks after keratoplasty, and the status of corneal transplants were observed when skin grafts were rejected.
RESULTS: Allografts in the CTLA4-FasL group (median survival time [MST] = 106 days, p = 0.0042) and the CsA DDS group (MST = 60 days, p = 0.0037) revealed extending survival time, compared with that in the untreated allograft group (MST = 14 days). There were significantly fewer CD4-positive T cells in both the isograft group and the CsA DDS group. In the untreated allograft group, the number of CD4+ T cells gradually increased from day 1 until the final day of observation (day 21). By contrast, it reached a peak on day 7 and then absolutely reduced in the CTLA4-FasL group. Many apoptotic cells were detected on day 7 in the CTLA4-FasL group, but very few were seen in the other groups. Within 30 days of skin-graft rejection, previously healthy and long-standing corneal grafts became rejected in the CsA DDS group but remained clear in the CTLA4-FasL group.
CONCLUSIONS: CTLA4-FasL can prolong the survival time of corneal allografts in mice, exerting a negative regulation on T-cell activation simultaneously by blocking B7 costimulatory signals and inducing Fas-FasL apoptotic pathway. Due to the adjunctive role of FasL, it also appears to be a potential activity of tolerance induction through T-cell apoptotic pathways.
METHODS: Orthotopic penetrating keratoplasty was performed on BALB/c mice. The mice were randomized into four groups: the isograft group, untreated allograft group, cyclosporine A drug delivery system (CsA DDS)-anterior chamber implanted group, and 10 microg/mL CTLA4-FasL-treated group. Allografts were from C57BL/6 mice. Survival time of corneal grafts was evaluated. Immunohistological method and TdT-mediated dUTP Nick End Labeling (TUNEL) were applied for the detection of CD4+ T cells and apoptotic cells in corneal transplants. To assess whether peripheral immune tolerance appeared after the treatment of CTLA4-FasL, CsA DDS-implanted- and CTLA4-FasL-treated BALB/c mice with clear grafts received skin allografts at 4 weeks after keratoplasty, and the status of corneal transplants were observed when skin grafts were rejected.
RESULTS: Allografts in the CTLA4-FasL group (median survival time [MST] = 106 days, p = 0.0042) and the CsA DDS group (MST = 60 days, p = 0.0037) revealed extending survival time, compared with that in the untreated allograft group (MST = 14 days). There were significantly fewer CD4-positive T cells in both the isograft group and the CsA DDS group. In the untreated allograft group, the number of CD4+ T cells gradually increased from day 1 until the final day of observation (day 21). By contrast, it reached a peak on day 7 and then absolutely reduced in the CTLA4-FasL group. Many apoptotic cells were detected on day 7 in the CTLA4-FasL group, but very few were seen in the other groups. Within 30 days of skin-graft rejection, previously healthy and long-standing corneal grafts became rejected in the CsA DDS group but remained clear in the CTLA4-FasL group.
CONCLUSIONS: CTLA4-FasL can prolong the survival time of corneal allografts in mice, exerting a negative regulation on T-cell activation simultaneously by blocking B7 costimulatory signals and inducing Fas-FasL apoptotic pathway. Due to the adjunctive role of FasL, it also appears to be a potential activity of tolerance induction through T-cell apoptotic pathways.
Предметные рубрики MeSH
AnimalsAntigens, CDAntigens, DifferentiationApoptosisCD4-Positive T-LymphocytesCTLA-4 AntigenCorneaCyclosporineDisease Models, AnimalFas Ligand ProteinFluorescent Antibody Technique, IndirectGraft SurvivalHumansImmunosuppressive AgentsIn Situ Nick-End LabelingKeratoplasty, PenetratingMaleMiceMice, Inbred BALB CMice, Inbred C57BLRecombinant Fusion ProteinsSkin TransplantationTransplantation, Homologous