Research on the suppressive effect on transplantation rejection by indoleamine 2, 3-dioxygenase]

To study the suppressive effect of indoleamine 2, 3-dioxygenase on transplantation rejection in mice heterotopic cardiac transplantation.Adenovirus vector containing IDO gene was used to infect donor (C57BL/6) DC to obtain IDO(+)DC. Mouse heterotopic cardiac transplantation models were established (C57BL/6-BALB/c) and the following groups were set up, including the control group, DC injection group, TC injection group, IDO(+)DC injection group and co-injection group of IDO(+)DC and TC, 12 donors and 12 recipients in each group.Survival time of the donor heart in every group was observed. Meanwhile, donor hearts were harvested 7 days post transplantation for different examinations, including pathological examination, mRNA expression of IDO through real-time PCR, IDO protein expression through Western blot. Peripheral blood of recipients was also harvested for CD3(+)T lymphocyte apoptosis rate examination through fluorescence-activated cell sorting.One-way ANOVA and Kaplan-Meier Survival Analysis were used for statistic analysis of IDO expression, CD3(+)T lymphocyte apoptosis rate and survival time of the donor heart respectively.Cadiac allograft median survival time of each group were 7.0, 7.5, 11.0, 17.5, 24.0 days respectively. Compared with control and DC injection group, IDO(+)DC, TC and co-injection group significantly prolonged the survival time of donor hearts (t = 3.523-8.449, P < 0.01). Both IDO mRNA and protein expression showed significant increase(t = 5.974-16.176, P < 0.01). The CD3(+)T lymphocyte apoptosis rate was also significantly increased (t = 6.324-38.120, P < 0.01). Compared with IDO(+)DC or TC group alone, co-injection group significantly prolonged the survival time of the donor heart (t = 5.971 and 2.831, P < 0.05). Both IDO mRNA and protein expression showed significant increase (t = 2.853-15.194, P < 0.01).Furthermore, the CD3(+)T lymphocyte apoptosis rate was significantly increased as well (t = 26.069 and 7.643, P < 0.05).Suppressive effect of co-injection of IDO(+)DC and TC is much more effective than administration of IDO(+)DC or TC alone, which suggests that IDO achieved immune suppressive effect through the pathway of tryptophan depletion and accumulation of TC.