Objective:To evaluate the immunosuppressive effect of monoclonal antibodies (McAb) against cell surface adhesion molecules on transplant rejection. Methods: C57BL/6 (H-2b) mouse cardiac grafts were transplanted into B...Objective:To evaluate the immunosuppressive effect of monoclonal antibodies (McAb) against cell surface adhesion molecules on transplant rejection. Methods: C57BL/6 (H-2b) mouse cardiac grafts were transplanted into BALB/c(H- 2d) mice. This model was used to investigate the possibility of immunosuppressive induction with CD44 McAb, leukocyte function associated antigen (LFA-1) and intercellular adhesion molecule (ICAM-1). Results: Treatment of the allograft recipients with CD44 McAb alone, or both LFA-1 and ICAM-1 or combination of these 3 McAb significantly prolonged the cardiac allografts survival as compared with PBS controls (P<0.01). The combination of anti-CD44 and ICAM-1 and LFA-1 McAb was shown to produce more significant prolongation of grafts survival than anti-CD44 McAb alone or both anti-ICAM- 1 and LFA-1 McAb (P < 0.01). Histological examination of the grafts treated with the McAb displayed greatly reduced mononuclear cell infiltration. The proliferation of spleen cells from recipient BALB/c with McAb treatment was significantly inhibited in response to the stimulators of C57BL/6 spleen cells, but increased upon the stimulation of C3H/He (H-2k) spleen cells, as demonstrated by mixed lymphocyte reaction. Similarly, the cytotoxic activity against donor H-2-compatible (H-2b) target cells, EL-4 cells, was significantly suppressed. The spleen cells from allografted recipient BALB/c mice with McAb treatment induced specific tolerance for C57BL/6 cardiac grafts in allografted recipients, whereas those from allografted BALB/c mice without McAb treatment induced acute rejection. Conclusion: These results indicate that antiadhesion therapy using a combination of McAb to adhesion molecules can induce specific immunosuppression of transplant rejection.展开更多
文摘Objective:To evaluate the immunosuppressive effect of monoclonal antibodies (McAb) against cell surface adhesion molecules on transplant rejection. Methods: C57BL/6 (H-2b) mouse cardiac grafts were transplanted into BALB/c(H- 2d) mice. This model was used to investigate the possibility of immunosuppressive induction with CD44 McAb, leukocyte function associated antigen (LFA-1) and intercellular adhesion molecule (ICAM-1). Results: Treatment of the allograft recipients with CD44 McAb alone, or both LFA-1 and ICAM-1 or combination of these 3 McAb significantly prolonged the cardiac allografts survival as compared with PBS controls (P<0.01). The combination of anti-CD44 and ICAM-1 and LFA-1 McAb was shown to produce more significant prolongation of grafts survival than anti-CD44 McAb alone or both anti-ICAM- 1 and LFA-1 McAb (P < 0.01). Histological examination of the grafts treated with the McAb displayed greatly reduced mononuclear cell infiltration. The proliferation of spleen cells from recipient BALB/c with McAb treatment was significantly inhibited in response to the stimulators of C57BL/6 spleen cells, but increased upon the stimulation of C3H/He (H-2k) spleen cells, as demonstrated by mixed lymphocyte reaction. Similarly, the cytotoxic activity against donor H-2-compatible (H-2b) target cells, EL-4 cells, was significantly suppressed. The spleen cells from allografted recipient BALB/c mice with McAb treatment induced specific tolerance for C57BL/6 cardiac grafts in allografted recipients, whereas those from allografted BALB/c mice without McAb treatment induced acute rejection. Conclusion: These results indicate that antiadhesion therapy using a combination of McAb to adhesion molecules can induce specific immunosuppression of transplant rejection.
