| Autor: |
Y-Y, Guo, C-J, Yin, M, Zhao, L-T, Guo, R-F, Su, X-X, Fu, W-L, Dong, X-B, Tan |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
European review for medical and pharmacological sciences. 23(21) |
| ISSN: |
2284-0729 |
| Popis: |
Corneal allograft rejection is an immunological hypersensitive reaction caused by the antigenicity of the donor cornea. This study aimed to explore the effects of RMT1-10 on the prevention of corneal graft rejection by modifying immunological characteristics of dendritic cells (DCs).DCs and CD4+T cells were sorted using flow cytometry and used for in vitro mixed lymphocyte culture. The cultured cells were prepared for the characterization of the DC cell phenotypes using the markers CD11c, CD80, MHC II, CD54, and TIM-4. Cytokine concentrations of IL-4, IL-12, and IL-10 of supernatants were measured by the enzyme-linked immunosorbent assay. CD4+T cells were examined by flow cytometry for apoptosis and proliferation. We also investigated the effect of RMT1-10 in the prevention and treatment of high-risk corneal graft rejection using a mouse model of corneal transplantation.DCs were identified as the CD11c+MHC-II-expressing subset. RMT1-10 suppressed the expression of CD11c, CD80, MHC II, CD54, and TIM-4 of DCs using the blockade of TIM-1 signaling. Moreover, TIM-1 blockade inhibited the production of IL-12 and IL-10 in a mixed lymphocyte culture system. However, a TIM-1 blockade had no effect on the apoptosis of CD4+T cells. RMT1-10 suppressed DC maturation, inhibiting the proliferation of CD4+T cells.RMT1-10 significantly improved the survival rate of the corneal allografts in mice compared with saline-injected controls. This clinical improvement from RMT1-10 occurred through the inhibition of CD4+T cell proliferation. Moreover, RMT1-10 induced antigen-specific detection of receptor immune tolerance. The cross-linking of TIM-1 on CD4+T cells with the agonist mAb provided a costimulatory inhibition signal for T cell activation or proliferation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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