Expression of CD80 on Cultured Neonatal Mice Cardiomyocytes and Attenuation of Cytotoxic T Lymphocyte–Mediated Lysis

Abstract

Transplantation of cultured heterogeneous proliferating cardiomyocytes is a promising therapeutic approach for the treatment of the damage cardiac area resulting from myocardial infarction. However, the chances of recipient rejection are high. How to reduce the immunogenicity of heterogeneous cardiomyocytes and attenuate immune rejection is one of the key stumbling blocks in the application of these cells. In this study, we determined that cultured neonatal cardiomyocytes from mice can express CD80 after culture. CD80 is one of the key costimulatory molecules. Most scholars believe that the main function of CD80 is to activate and boost immune rejection. However, recent studies have shown that CD80 may primarily bind with CTLA-4 and inhibit the immune response. To further study how CD80 worked on these cells, a cytotoxic T-lymphocyte (CTL) assay was performed. The results showed that activated allogenic CTLs lysed cultured cardiomyocytes lacking CD80 expression, but they did not efficiently lyse cardiomyocytes expressing CD80. If we blocked the CD80 with anti-CD80 monoclonal antibody (mAb), the percentages of cardiomyocytes lysis were significantly increased. CD80 can bind CD28, CTLA-4, PD-L1, and even B7-H1, but the main ligands are CD28 and CTLA-4. Thus, we blocked the two ligands separately. When anti-CTLA-4 mAb was applied, the percentages of cardiomyocytes lysis were significantly increased, but when anti-CD28 mAb was applied, the percentages of cell lysis were the same as the intact control. The results indicated that CD80 and CTLA-4 played an important role on the attenuation of CTL-mediated lysis. To our knowledge, this study, for the first time, proves that cardiomyocytes can express CD80 and this expression pattern can resist CTL-mediated lysis through CTLA-4 pathway. The results could have implications in efforts to improve therapeutic strategies for cardiomyocyte transplantation.