Korean J Transplant.  2023 Nov;37(Suppl 1):S203. 10.4285/ATW2023.F-7922.

Combined use of tocilizumab (IL-6 receptor blocking antibody) and mesenchymal stem cells attenuate the development of anti-HLA-A2.1 antibody in highly sensitized mice model

• Fang X
• Cui S
• Lee H
• Kim HD
• Lim SW
• Oh EJ
• Yang CW
• Shin YJ
• Chung BH

• KMID: 2551823
• DOI: http://doi.org/10.4285/ATW2023.F-7922

Abstract

The aim of this research to investigate the synergistic effects of IL-6 receptor blocking antibody (tocilizumab [TCZ]) and bone marrow derived mesenchymal stem cells (BM-MSCs) on the humoral immune responses of an allo-sensitized mouse model developed using HLA.A2 transgenic mice. Wild-type C57BL/6 mice were sensitized with skin allografts from C57BL/6-Tg (HLA-A2.1)1Enge/J mice and were treated with either TCZ or BM-MSC or both TCZ and BM-MSC. HLA.A2-specific immunoglobulin G (IgG) was reduced in all of TCZ, BM-MSC and TCZ+BM-MSC in comparison with allo-sensitized control group, and it was the most significant in TCZ+BM-MSC group. Combined use of TCZ and BM-MSC also resulted in the increased pre-pro B cells and decreased immature and mature B cell proportions in the BM (P<0.05 vs. control) than other groups. In the spleen, an increase in transitional, memory, and long-lived plasma B cells was observed with a significant decrease in marginal and follicular B cells (P<0.05 vs. control) in TCZ+BM-MSC group. In conclusion, combined use of TCZ and BM-MSC inhibit B cell differentiation and maturation in spleen and BM and finally resulting in the reduction of HLA.A2-specific IgG in highly sensitized mice model. Our data suggests that combined use of TCZ and BM-MSC may serve as a useful future strategy for desensitization therapy.