HLA-DRB5 overexpression promotes platelet reduction in immune thrombocytopenia mice model by facilitating MHC-II-mediated antigen presentation

Acta Haematol. 2024 May 14. doi: 10.1159/000538749. Online ahead of print.

Abstract

Introduction: 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.

Methods: 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 haematology analyzer. MHC-II/CD80/CD86 expression in mice blood was measured by quantitative Real Time (qRT)-PCR and immunofluorescence assay. CD8+ T cell proportion in mice blood was detected by flow cytometry.

Results: 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.

Conclusion: HLA-DRB5 overexpression upregulates MHC-II-mediated antigen presentation to CD8+ T cells, thus lowering PLT count in the ITP mice model.