Observation Of The Effect Of Anti-CD45RB Combined With Anti-TIM-1 In The Treatment Of Acute Graftversus-host Disease

Anti-CD45 RB and anti-TIM-1 monoclonal antibodies,as commonly used immunosuppressive agents in recent years,can induce long-term tolerance of grafts in the transplantation of mouse heart and pancreatic islets.In recent years,co-transplantation of donor bone marrow stem cells is one of the most effective methods for inducing transplant immune tolerance,but bone marrow transplantation is prone to cause graft-versus-host disease.On the basis of previous research,this experiment explored the therapeutic effects of anti-CD45 RB and anti-TIM-1 monoclonal antibodies on acute graft-versus-host disease.The purpose of this experiment is to construct a mouse model of acute graft-versushost disease,explore the therapeutic effects of anti-CD45 RB and anti-TIM-1 on acute graft-versus-host disease,and analyze the tissue damage of the target organs of acute graftversus-host disease.Finally,the expression of B cells,Breg cells,T cells,Treg cells and other immune cells were detected by flow cytometry.Irradiate the mice by total body irradiation with a single dose of 8 Gy of γ-ray,then inject allogeneic bone marrow and spleen cells into the recipient mice.Inject antiCD45 RB and anti-TIM-1 antibodies into the mice in the treatment group,monitor the survival of the mice in the treatment group and the non-treatment group,and perform clinical scores on the severity of aGvHD in the mice;Flow cytometry was used to analyze the classification and proportion of H2 Kb cells,B cells,T cells,Breg cells and Treg cells in the recipient mice,so as to analyze the chimerism and inflammation of the mice.The pathological analysis of aGvHD target organs was performed by HE staining.Compared with the non-treatment group,the survival time and clinical score of the treatment group didn’t improve significantly,and the antibody hadn’t obvious therapeutic effect on acute graft-versus-host disease induced by bone marrow transplantation.Because radiation severely damages the recipient’s immune system,most of the lymphocytes in the recipient are derived from donor mice.The proportion of Breg cells in the antibody treatment group increased,but the proportion of Treg cells decreased significantly,and Treg plays an important role in relieving the symptoms of aGvHD.We have showed that anti-CD45 RB in combination with anti-TIM-1 antibody had a synergistic effect.This effect depends on the presence of recipient B cells.However,pretreatment results in severe loss of recipient B lymphocytes.The target organ inflammation of acute graft-versus-host disease will worsen over time.Anti-CD45 RB and anti-TIM-1 antibodies can effectively induce transplant tolerance in heart and pancreatic islet transplantation.But it cannot reduce the side effects of bone marrow transplantation,namely graft-versus-host disease.This result is closely related to the pretreatment process.Myeloablative pretreatment completely destroyed the immune system of the recipient mice and severely lost B lymphocytes.This leads to a sharp decrease in recipient B cells.In addition,the immune tolerance of Breg cells depends on the interaction with Treg cells,so the decline of Treg cells will also lead to the failure of antibody treatment.