Influence of B7/CD28 and CD40/CD154 co-stimulation signal pathway blockage on immune function and hematopoietic stem cell transplantation in sensitized mice

To investigate the influence of B7/CD28 and CD40/CD154 co-stimulation signal pathway blockage on immune function as well as the regeneration of hematopoietic stem cells in sensitized mouse recipients. The co-stimulation signal pathway was blocked by CTLA4Ig and/or anti-CD154 monoclonal antibody. The numbers of B and T cells were determined using flow cytometry. The immune status and hematopoietic reconstitution in sensitized recipients were also investigated. Flow cytometry results showed that the numbers of B cells, memory T cells, and effector T cells in sensitized mice were significantly higher than that in the normal control mice. CTLA4Ig and/or anti-CD154 monoclonal antibody significantly inhibited the activation of B and T cells with a synergistic effect. The number of fluorescence-labeled HSCs from the donors in the bone marrow in control group and the combinative treatment of CTLA4Ig and anti-CD154 group gradually increased after HSCT. In addition, the chimeric rate of H-2D(b+) cells was over 90% after the HSCT, suggesting completed bone marrow reconstruction. Blocking the co-stimulation signal pathway induced immune tolerance in sensitized mice. CTLA4Ig and anti-CD154 promoted the homing and engraftment of hematopoietic stem cells, induced immune tolerance and hematopoietic reconstitution, and increased the survival of sensitized mouse recipients.