J2对同种异体穿透性角膜移植模型大鼠CD4+和CD8+T细胞免疫功能的抑制

J2 inhibits immune function of CD4+ and CD8+ T cells in allogeneic penetrating keratoplasty rat models

BACKGROUND: J2 takes functional domain (MHC CD4-D1/) of complex conjugate of CD4 molecule and MHC class II molecule as a target, and is a small molecule compound obtained by computer screening from a chemical data containing hundreds of thousands of organic compounds. In the previous study, J2 was used in mouse models of skin transplantation and keratoplasty by oral and intraperitoneal injection. Results verified that J2 could prolong the survival time of grafts, and suppress occurrence of rejection. To better play the role of a drug targeting and to reduce systemic toxicity, J2 will be further utilized in local treatment of keratoplasty rejection. OBJECTIVE: To investigate the inhibitory effect of new immunosuppressive agent J2 on CD4+ and CD8+ T cell immune functions in rat models receiving allogenic penetrating keratoplasty. METHODS: Allogeneic penetrating keratoplasty model was established using the adult female Wistar rats as donors and Sprague-Dawley rats as recipients. Group A: normal Sprague-Dawley rats were injected with 0.05 mL placebo subconjunctivally. Surgery rats were randomly divided into three groups. Group B: allograft rats were injected with 0.05 mL placebo subconjunctivally after autologous keratoplasty. Group C: allograft rats were injected with 0.05 mL placebo subconjunctivally. Group D: allograft rats were injected with 1% J2-nanosuspension 0.05 mL subconjunctivally. The distribution of T cell subsets in peripheral blood was detected using flow cytometry at 3 days, 1, 2 and 3 weeks after transplantation and compared among groups.  RESULTS AND CONCLUSION: There was no significant difference in total CD3+ T cells, CD4+ T cells, CD8+ T cells and CD4+/CD8+ in peripheral blood lymphocytes in group B at various time points. At 3 days and 1 week after surgery in group C, no significant difference in total CD3+ T cells, CD4+ T cells and CD8+ T cells was detected. At 1 and 2 weeks, the number of total CD3+ T cells, CD4+ T cells and CD8+ T cells increased, showing significant differences (P < 0.05). In group D, no significant hyperplasy was found in CD4+ T cells and CD8+ T cells at 1 and 2 weeks. The horizontal comparison of the same time point: the total CD3+ T lymphocytes of group D was significantly less than group C at 3 days, 1 and 2 weeks after operation (P < 0.05), whereas there was no significant difference at 3 weeks between the group D and group C. The number of CD4+ T lymphocytes in group D was less than in group C at 3 days and 1 week, but with no significant difference. The ratio of CD4+/CD8+ had no significant difference in group D compared with group C at 3 days, 1 and 3 weeks. J2 inhibits T lymphocyte proliferation and then inhibits T cell-mediated corneal allograft rejection.