Objective.The purpose of this study was to assess the renal graft expression of ICAM 1(intercellular adhesion molecule 1) and LFA 1(lymphocyte function associated antigen 1)molecule with rela...Objective.The purpose of this study was to assess the renal graft expression of ICAM 1(intercellular adhesion molecule 1) and LFA 1(lymphocyte function associated antigen 1)molecule with relation to graft rejection. Methods.Rat kidney transplantation was performed according to the procedure of Kamada with some modification.Experimental rats were divided into 5 groups.The survival time of recipient rats and function of grafts after renal transplantation were observed.The sections of renal graft were stained for monoclonal antibody ICAM 1 and LFA 1, and then quantification of ICAM 1 and LFA 1 expression was accomplished by computer image analysis. Results.ICAM 1 and LFA 1 increased significantly in the renal allograft rejection group as compared with the non rejection groups(P<0 05). Conclusion.Both biopsy of renal graft and monitoring of ICAM 1 and LFA 1 are useful tools in diagnosing and treating acute rejection.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
The aim of this study is to find the experimental evidence that the precursor frequency of alloreactive CTLs is proportional to the number of the T-cell epitope specificities. The number of T-cell epitope specificitie...The aim of this study is to find the experimental evidence that the precursor frequency of alloreactive CTLs is proportional to the number of the T-cell epitope specificities. The number of T-cell epitope specificities was manipulated by pulsing different humor of HLA-A2 restricted peptide（s） onto the T2 cells, which acted as stimulating cells to elicit allo-reaction by co-culturing with peripheral blood lymphocytes （PBLs） of HLA-A2 negative individual. Ten HLA-A2 restricted peptides （all were normal cell components ） were synthesized, and cell peptide extract was prepared by frozen and thawed. T2 cells loaded with different number of peptide（s） were co-cultured with PBLs of an HLA-A2 negative individual; the latter were stained with PKH67 in advance. Then the proliferation was monitored with flow cytometry, and the precursor frequency of the effector cells was ＇analyzed by the ModFit Software. After 6 d of culture, no proliferation was observed in the bulk culture of PBL alone, and obvious proliferation took place when PBLs of the HLA-A2 negative were co-cultured with T2 cells loaded with or without loading peptide（ s）. The precursor frequency of the alloreactive CTLs was 0.052 819 for co-culture with T2 cells loaded without peptide; however it was 0. 030 429 for T2 cells with EBV/LMP2A and 0. 030 528 for T2 cells loaded with a single autogeneic peptide, and increased up to 0. 144 942 for T2 cells loaded with 10 autogeneic peptides; the precursor frequency was 0. 203 649 when co-cultured with T2 cells loaded with miscellaneous peptides extracted from the cytoplasm of T2 cells. This study reveals that the precursor frequency of alloreactive CTLs is proportional to the number of T-cell epitope specificities, and independent of the density of the allogeneic HLA Class Ⅰ molecule. Our findings support the hypothesis that the alloreactive T cell populations comprise miscellaneous T cell clones; each is specific to corresponding pMHC. The novel constellation of peptides presented by allogeneic MHC molecules makes thousands of different epitopes, which account for the exceptional high precursor frequency of alloreactive T cells.展开更多
文摘Objective.The purpose of this study was to assess the renal graft expression of ICAM 1(intercellular adhesion molecule 1) and LFA 1(lymphocyte function associated antigen 1)molecule with relation to graft rejection. Methods.Rat kidney transplantation was performed according to the procedure of Kamada with some modification.Experimental rats were divided into 5 groups.The survival time of recipient rats and function of grafts after renal transplantation were observed.The sections of renal graft were stained for monoclonal antibody ICAM 1 and LFA 1, and then quantification of ICAM 1 and LFA 1 expression was accomplished by computer image analysis. Results.ICAM 1 and LFA 1 increased significantly in the renal allograft rejection group as compared with the non rejection groups(P<0 05). Conclusion.Both biopsy of renal graft and monitoring of ICAM 1 and LFA 1 are useful tools in diagnosing and treating acute rejection.
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.
基金The work was supported by the grants from the National Natural Science Foundation of China(No.30271201)the Major State Basic Research Development Program of China(No.2001C510008).
文摘The aim of this study is to find the experimental evidence that the precursor frequency of alloreactive CTLs is proportional to the number of the T-cell epitope specificities. The number of T-cell epitope specificities was manipulated by pulsing different humor of HLA-A2 restricted peptide（s） onto the T2 cells, which acted as stimulating cells to elicit allo-reaction by co-culturing with peripheral blood lymphocytes （PBLs） of HLA-A2 negative individual. Ten HLA-A2 restricted peptides （all were normal cell components ） were synthesized, and cell peptide extract was prepared by frozen and thawed. T2 cells loaded with different number of peptide（s） were co-cultured with PBLs of an HLA-A2 negative individual; the latter were stained with PKH67 in advance. Then the proliferation was monitored with flow cytometry, and the precursor frequency of the effector cells was ＇analyzed by the ModFit Software. After 6 d of culture, no proliferation was observed in the bulk culture of PBL alone, and obvious proliferation took place when PBLs of the HLA-A2 negative were co-cultured with T2 cells loaded with or without loading peptide（ s）. The precursor frequency of the alloreactive CTLs was 0.052 819 for co-culture with T2 cells loaded without peptide; however it was 0. 030 429 for T2 cells with EBV/LMP2A and 0. 030 528 for T2 cells loaded with a single autogeneic peptide, and increased up to 0. 144 942 for T2 cells loaded with 10 autogeneic peptides; the precursor frequency was 0. 203 649 when co-cultured with T2 cells loaded with miscellaneous peptides extracted from the cytoplasm of T2 cells. This study reveals that the precursor frequency of alloreactive CTLs is proportional to the number of T-cell epitope specificities, and independent of the density of the allogeneic HLA Class Ⅰ molecule. Our findings support the hypothesis that the alloreactive T cell populations comprise miscellaneous T cell clones; each is specific to corresponding pMHC. The novel constellation of peptides presented by allogeneic MHC molecules makes thousands of different epitopes, which account for the exceptional high precursor frequency of alloreactive T cells.
