.cd28/ctla4-b7 T-cell Costimulatory Pathway And Immunology Of Mab Of Cd28 And Its Fab Fragment Immunosuppression Mechanism Of Experimental Research

The activation of T cells to differentiate and to proliferate is an essential step in the immune response to antigen, especially in cell-mediated acute allograft rejection. Now it is believed that the activation of T cells responding to foreign antigen requires the interaction of CD3/TCR complex with Ag/MHC complex presented on antigen-presenting cells. However, recent studies demonstrate that signals transmitted via this pathway are not sufficient to generate a complete T-cell activation and proliferation but require a second costimulatory signal. CD28 molecule, a 44-Kdal polypeptide, expressed on T cells has been shown to serve as a surface component of a signal transduction pathway that can provide costimulatory signal. CTLA-4, a homologous molecule to CD28, has a similar genomic organization and biological function. B7, the corresponding ligand to CD28/CTLA-4, is present on the surface of macrophages, dendritic cells and activated B cell. The interaction of CD28/CTLA-4 and B7 is a major costimulatory pathway for T cell activation. This pathway is CsA-independent and not associated with T cell receptors. Inhibition of this pathway results in development of antigen-specific unresponsiveness and clonal anergy. CTLA4-Ig, a chimeric fusion protein between extracellular domain of human CTLA-4 and an immunoglobulin IgG1 constant region, can block the interaction between CD28/CTLA4 and B7 and has been shown to inhibit T cell proliferation in vitro and prolong allograft survival time or infinitive survive in vivo. Immunosuppression induced by blocking CD28/CTLA4-B7 pathway is distinct from that induced by CsA. So investigators have being carried out a lot of works in this field to look forword creating a new concept in transplantation tolerance.In present study, the biologic function of anti-CD28 monoclonal antibody and its Fab fragment were investigated in vitro and in vivo.Initially, in vitro experiments were performed using mAbCD28 and its Fab fragments in two-way mixed lymphocyte reaction between Balb/c and C57BL mice. Results showed that mAbCD28 and its Fab fragments were effective in inhibiting MLR in a dose-dependent fashion compared with the control IgG.Based on the results of MLR, we tested the effects of mAbCD28 and its Fab fragments in Wistar→Wistar and SD→Wistar parathyroid gland allografts.