小鼠人白细胞抗原异基因皮肤移植后的机体免疫应答

目的 探讨人白细胞抗原(HLA)致敏后机体免疫应答,为寻找有效手段阻断抗体介导排斥反应(AMR)提供实验依据.方法 以转HLA-A2.1基因小鼠为供体,野生型小鼠为受体行2次皮肤移植建立HLA致敏小鼠模型,观察致敏小鼠体内各种免疫应答变化.结果 皮肤移植致敏后小鼠体内IgG显著升高,28 d达高峰(14.10±0.47μg/L,酶联免疫吸附试验(ELISA)],以IgG2a为主(449.4±113.5)μg/L,莱姆德抗原板法],伴外周血、脾脏及骨髓中各种淋巴细胞组成的变化;2次移植皮肤存活天数较第1次显著缩短(3.0±0.7)d比(10.0±1.3)d];HLA-A2单一抗原致敏可诱导产生多种抗体,并对表达HLA-A2靶细胞具细胞毒作用.结论 HLA-A2致敏可诱导受体产生高水平IgG2a,与多种Ⅰ类HLA存在交叉反应,伴有B及T淋巴细胞的激活,导致移植后受体发生AMR.

Abstract：

Objective To understand the immune response changes in human leukocyte antigens (HLA) sensitized individuals in order to find out effective treatment for antibody-mediated rejection (AMR). Methods A HLA sensitized mouse model was established by skin graft using HLA-A2. 1 transgenic mice as donors and wild type mice as recipients. Different immune responses were studied in the sensitized recipients. Results Sensitizing mice with skin grafts from HLA-A2. 1 transgenic mice resulted in robust production of anti-HLA IgG, peak in 28 d( 14. 10 ±0. 47) μg/L, enzyme linked immunosorbent assay (ELISA)], mainly IgG2a(449. 4 ± 113.5) μg/L, LATM120], accompanied by changes in the constitution of different B and T lymphocytes in peripheral blood, spleen, and bone marrow, also accelerated rejection of a secondary skin allograft2nd graft survival day (3.0 ± 0. 7 ) d vs 1 st graft survival day ( 10. 0 ± 1.3 ) d]. Sensitization of recepients with single HLA-A2 induced antibodies which had cross reaction with a panel of class Ⅰ HLA. These antibodies had cytotoxic effect targeting HLA-A2 expressing cells.Conclusion HLA-A2 sensitization resulted in abundant production of IgG2a accompanied by activation and proliferation of different B and T lymphocytes. These antibodies cross-reacted with a panel of class Ⅰ HLA, and may be the cause of AMR after allogenic skin graft.

The immune response changes after human leukocyte antigens allogenic skin graft in mice

Objective To understand the immune response changes in human leukocyte antigens (HLA) sensitized individuals in order to find out effective treatment for antibody-mediated rejection (AMR). Methods A HLA sensitized mouse model was established by skin graft using HLA-A2. 1 transgenic mice as donors and wild type mice as recipients. Different immune responses were studied in the sensitized recipients. Results Sensitizing mice with skin grafts from HLA-A2. 1 transgenic mice resulted in robust production of anti-HLA IgG, peak in 28 d( 14. 10 ±0. 47) μg/L, enzyme linked immunosorbent assay (ELISA)], mainly IgG2a(449. 4 ± 113.5) μg/L, LATM120], accompanied by changes in the constitution of different B and T lymphocytes in peripheral blood, spleen, and bone marrow, also accelerated rejection of a secondary skin allograft2nd graft survival day (3.0 ± 0. 7 ) d vs 1 st graft survival day ( 10. 0 ± 1.3 ) d]. Sensitization of recepients with single HLA-A2 induced antibodies which had cross reaction with a panel of class Ⅰ HLA. These antibodies had cytotoxic effect targeting HLA-A2 expressing cells.Conclusion HLA-A2 sensitization resulted in abundant production of IgG2a accompanied by activation and proliferation of different B and T lymphocytes. These antibodies cross-reacted with a panel of class Ⅰ HLA, and may be the cause of AMR after allogenic skin graft.