Background This study was to evaluate whether anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro and prolong cardiac allograft...Background This study was to evaluate whether anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro and prolong cardiac allograft survival after adoptive transfer KH*2/5DMethods Anergic cells were induced in vitro by the addition of anti-CD154 and anti-CD80 monoclonal antibodies (mAbs) to primary MLR (mixed lymphocyte reaction) consisting of BALB/c as responder and C3H as stimulator Anergic cells were added to a newly formed MLR in assessing the regulatory capacity and antigen specificity of anergic cells The ability of anergic cells to respond to antigen and/or exogenous recombinant mouse interleukin-2 (rmIL-2) was tested For in vivo studies, anergic cells were intravenously injected into 3 0-Gy γ-irradiated BALB/c mice immediately after heterotopic abdominal cardiac transplantation To prolong allograft survival, recipient mice injected with anergic cells received rapamycin therapy (1 mg·day -1 ·kg -1 ) KH*2/5DResults Anergic cells strongly suppressed the proliferation of naǐve BALB/c splenocytes against the original (C3H) stimulator in a dose-dependent manner, but they failed to suppress the proliferation of naǐve BALB/c splenocytes against the third-party (C57BL/6J) stimulator The anergic state was reversed by both original (C3H) stimulator and additional exogenous IL-2 In in vivo studies, untreated irradiated BALB/c mice rejected C3H cardiac allografts with a mean survival time of (8 6±1 1) days, whereas those injected with the anergic cells rejected the allografts with a mean survival time of (11 8±1 9) days, which was slightly longer than that of the untreated mice The protocol based on anergic cells injection plus rapamycin therapy could prolong allograft survival significantly [(29 6±4 4) days] Conclusions Anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro , and prolong cardiac allograft survival after adoptive transfer in the presence of rapamycin therapy This procedure might be clinically useful for prolonging allograft survival if optimal protocols are developed展开更多
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. Besides the int...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. Besides the interaction of CD3/TCR complex with Ag/MHC complex presented on antigen presenting cells, a complete T cell activation and proliferation requires a second costimulatory signal. The interaction of CD28/CTLA 4 and B7 is a major costimulatory pathway for T Cell activation. Inhibition of this pathway results in development of antigen specific unresponsiveness and clonal anergy.In present study,the biologic function of anti CD28 monoclonal antibody and its Fab fragment were investigated in vitro and in vivo.The results indicate that mAbCD28 and its Fab fragments could promote the functional recovery of allografts and prolong the graft survival,but could not reverse the acute rejection or induce transplantation tolerance in the rat PTG allograft model. We also found that peripheral TNF α level and NK cell activity were suppressed in the presence of mAbCD28 and its Fab fragments for a relatively long time after PTG transplantation.展开更多
Background OX40/OX40 ligand （OX40/OX40L） and programmed death-1/programmed death ligand-1 （PD-1/PD-L1） co- stimulator/signals play important roles in T cell-induced immune responses. The aim of this study was to i...Background OX40/OX40 ligand （OX40/OX40L） and programmed death-1/programmed death ligand-1 （PD-1/PD-L1） co- stimulator/signals play important roles in T cell-induced immune responses. The aim of this study was to investigate the roles of OX40/OX40L and PD-1/PD-L1 costimulatory pathways in mouse islet allograft rejection. Methods Lentiviral vectors containing OX40L siRNA sequences and an adenovirus vector containing the PD-L1 gene were constructed. The streptozotocin-induced model of diabetes was established in C57BL/6 （H-2b） mice. Diabetic C57BL/6 mice were randomly allocated into five groups： group 1, untreated control; group 2, Ad-EGFP treatment; group 3, Ad-PD-L1 treatment; group 4, OX40L-RNAi-LV treatment; group 5, OX40L-RNAi-LV combined with Ad-PD-L1 treatment. Lentiviral vector and the adenovirus vector were injected, singly or combined, into the caudal vein one day before islet transplantation. The islets of DBA/2 （H-2d） mice were transplanted into the renal subcapsular space of the diabetic recipients. Recipient blood glucose and the survival time of the allografts were monitored. Antigen-specific mixed lymphocyte reaction was also evaluated.展开更多
文摘Background This study was to evaluate whether anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro and prolong cardiac allograft survival after adoptive transfer KH*2/5DMethods Anergic cells were induced in vitro by the addition of anti-CD154 and anti-CD80 monoclonal antibodies (mAbs) to primary MLR (mixed lymphocyte reaction) consisting of BALB/c as responder and C3H as stimulator Anergic cells were added to a newly formed MLR in assessing the regulatory capacity and antigen specificity of anergic cells The ability of anergic cells to respond to antigen and/or exogenous recombinant mouse interleukin-2 (rmIL-2) was tested For in vivo studies, anergic cells were intravenously injected into 3 0-Gy γ-irradiated BALB/c mice immediately after heterotopic abdominal cardiac transplantation To prolong allograft survival, recipient mice injected with anergic cells received rapamycin therapy (1 mg·day -1 ·kg -1 ) KH*2/5DResults Anergic cells strongly suppressed the proliferation of naǐve BALB/c splenocytes against the original (C3H) stimulator in a dose-dependent manner, but they failed to suppress the proliferation of naǐve BALB/c splenocytes against the third-party (C57BL/6J) stimulator The anergic state was reversed by both original (C3H) stimulator and additional exogenous IL-2 In in vivo studies, untreated irradiated BALB/c mice rejected C3H cardiac allografts with a mean survival time of (8 6±1 1) days, whereas those injected with the anergic cells rejected the allografts with a mean survival time of (11 8±1 9) days, which was slightly longer than that of the untreated mice The protocol based on anergic cells injection plus rapamycin therapy could prolong allograft survival significantly [(29 6±4 4) days] Conclusions Anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro , and prolong cardiac allograft survival after adoptive transfer in the presence of rapamycin therapy This procedure might be clinically useful for prolonging allograft survival if optimal protocols are developed
文摘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. Besides the interaction of CD3/TCR complex with Ag/MHC complex presented on antigen presenting cells, a complete T cell activation and proliferation requires a second costimulatory signal. The interaction of CD28/CTLA 4 and B7 is a major costimulatory pathway for T Cell activation. Inhibition of this pathway results in development of antigen specific unresponsiveness and clonal anergy.In present study,the biologic function of anti CD28 monoclonal antibody and its Fab fragment were investigated in vitro and in vivo.The results indicate that mAbCD28 and its Fab fragments could promote the functional recovery of allografts and prolong the graft survival,but could not reverse the acute rejection or induce transplantation tolerance in the rat PTG allograft model. We also found that peripheral TNF α level and NK cell activity were suppressed in the presence of mAbCD28 and its Fab fragments for a relatively long time after PTG transplantation.
文摘Background OX40/OX40 ligand （OX40/OX40L） and programmed death-1/programmed death ligand-1 （PD-1/PD-L1） co- stimulator/signals play important roles in T cell-induced immune responses. The aim of this study was to investigate the roles of OX40/OX40L and PD-1/PD-L1 costimulatory pathways in mouse islet allograft rejection. Methods Lentiviral vectors containing OX40L siRNA sequences and an adenovirus vector containing the PD-L1 gene were constructed. The streptozotocin-induced model of diabetes was established in C57BL/6 （H-2b） mice. Diabetic C57BL/6 mice were randomly allocated into five groups： group 1, untreated control; group 2, Ad-EGFP treatment; group 3, Ad-PD-L1 treatment; group 4, OX40L-RNAi-LV treatment; group 5, OX40L-RNAi-LV combined with Ad-PD-L1 treatment. Lentiviral vector and the adenovirus vector were injected, singly or combined, into the caudal vein one day before islet transplantation. The islets of DBA/2 （H-2d） mice were transplanted into the renal subcapsular space of the diabetic recipients. Recipient blood glucose and the survival time of the allografts were monitored. Antigen-specific mixed lymphocyte reaction was also evaluated.
