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

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 allograft[2nd 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. Key words: Skin graft; Immune response; Anti-HLA antibody