HLA-DRB5 Overexpression Promotes Platelet Reduction in Immune Thrombocytopenia Mice Model by Facilitating MHC-II-Mediated Antigen Presentation

Abstract

<b><i>Introduction:</i></b> Major histocompatibility complex II (MHC-II)-mediated antigen presentation contributes to the pathogenesis of immune thrombocytopenia (ITP). Human leukocyte antigen (HLA)-DRB5 is an MHC-II molecule and this study aims to investigate its role and mechanisms in ITP development. <b><i>Methods:</i></b> Guinea pig anti-mouse platelet (PLT) serum-induced ITP mice received tail vein injection of HLA-DRB5 overexpressing adenoviral vector/immune receptor expressed on myeloid cells-1 (IREM-1) monoclonal antibody (mAb). PLT count changes in mice blood were assessed by a hematology analyzer. MHC-II/CD80/CD86 expression in mice blood was measured by quantitative real-time-PCR and immunofluorescence assay. CD8⁺ T-cell proportion in mice blood was detected by flow cytometry. <b><i>Results:</i></b> HLA-DRB5 overexpression exacerbated PLT reduction since the 5th day of the establishment of ITP mice model and enhanced MHC-II/CD80/CD86 expression upregulation as well as CD8⁺ T-cell ratio elevation in the blood of ITP mice, while its effects were reversed by IREM-1 mAb. <b><i>Conclusion:</i></b> HLA-DRB5 overexpression upregulates MHC-II-mediated antigen presentation to CD8⁺ T cells, thus lowering PLT count in the ITP mice model.