Animals ; Graft Rejection ; immunology ; Liver Transplantation ; Male ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sertoli Cells

Sertoli cells (SC) are known to contain immunoprotective properties, which allow them to survive as allografts without the use of immunosuppressive drugs. Experiments were designed to determine which factors are related to prolonged survival of allogeneic SC. Balb/c derived Sertoli (TM4) and colon cancer (CT-26) cell lines were implanted beneath the kidney capsule of non-immunosuppressed C57BL/6 mice and compared their survival as allografts. Compared to TM4 graft, which survived more than 7 days after transplantation, CT-26 showed massive infiltration of polymorphonuclear cells, necrosis and enlargement of draining lymph nodes. Cultured cell lines showed no differences in their expression patterns of FasL, TGF beta1, clusterin and two complement regulatory proteins (CRP, i.e., membrane cofactor protein, MCP; decay accelerating factor, DAF), but protectin (CD59), another member of CRP was expressed only on TM4. These results suggest that CD59 and unknown factors may contribute to the prolonged survival of SC in non-immunoprivileged sites.
Transplantation, Homologous/immunology ; Transforming Growth Factor beta1/*immunology ; Sertoli Cells/*immunology/*transplantation ; Mice, Inbred C57BL ; Mice ; Male ; Graft Survival/*immunology ; Female ; Fas Ligand Protein/*immunology ; Complement System Proteins/*immunology ; Clusterin/*immunology ; Cells, Cultured ; Cell Survival ; Animals

OBJECTIVETo study the protective role of Sertoli cell expressing FasL and CTLA-4Ig on allogeneic renal cell.

METHODSTesticular Sertoli cell and renal cell were prepared by digestion with enzymes. About 106 cells were injected into the subrenal capsule of allogeneic rats. 36 rats were divided into 3 groups: control group (10), co-transplantation group (16) and co-transplantation collaborated with CTLA-4Ig group (CTLA group, 10). Levels of serum IL-2 were tested on the 1st, 7th, 14th, 20th day after transplantation. The kidney was extracted on the 20th day. The survival of renal cells was determined by the Avidin Biotin Peroxidase Complex Technique (ABC); the brightness of grafts was measured by MD-20 image analysis system. Apoptosis within the grafts was observed with Terminal Deoxynucleotidyl Transferase-mediated X-dUTP Nick end Labeling (TUNEL) method.

RESULTSThe survival of renal cells in control group, co-transplantation group and CTLA group was 0, 14 and 10 respectively; The brightness values of co-transplantation group and CTLA group were 0.362 +/- 0.017 and 0.445 +/- 0.021, and the statistic differences between them were significant. Levels of serum IL-2 in CTLA group were lower compared with co-transplantation group, there being significant differences as well; Apoptosis of lymphocyte was observed within the grafts.

CONCLUSIONSSertoli cell and CTLA-4Ig have coordinative protective effect on allogeneic renal cell.

Abatacept ; Animals ; Antibodies ; Antigens, CD ; Antigens, Differentiation ; immunology ; CTLA-4 Antigen ; Immune Tolerance ; Immunoconjugates ; Kidney ; cytology ; Kidney Transplantation ; immunology ; Lymphokines ; Male ; Rats ; Rats, Wistar ; Sertoli Cells ; immunology

The understanding of main mechanisms that determine the ability of immune privilege related to Sertoli cells (SCs) will provide clues for promoting a local tolerogenic environment. In this study, we evaluated the property of humoral and cellular immune response modulation provided by porcine SCs. Porcine SCs were resistant to human antibody and complement-mediated formation of the membrane attack complex (38.41+/-2.77% vs. 55.02+/-5.44%, p=0.027) and cell lysis (42.95+/-1.75% vs. 87.99 +/-2.25%, p<0.001) compared to immortalized aortic endothelial cells, suggesting that porcine SCs are able to escape cellular lysis associated with complement activation by producing one or more immunoprotective factors that may be capable of inhibiting membrane attack complex formation. On the other hand, porcine SCs and their culture supernatant suppressed the up-regulation of CD40 expression (p<0.05) on DCs in the presence of LPS stimulation. These novel findings, as we know, suggest that immune modulatory effects of porcine SCs in the presence of other antigen can be obtained from the first step of antigen presentation. These might open optimistic perspectives for the use of porcine SCs in tolerance induction eliminating the need for chronic immunosuppressive drugs.
Animals ; Antibodies, Heterophile/immunology ; Antibody Formation/*immunology ; Antigens, CD40/immunology ; Aorta/cytology ; Cell Line, Transformed ; Cell Survival/immunology ; Complement Membrane Attack Complex/immunology ; Complement System Proteins/immunology ; Dendritic Cells/cytology/immunology ; Endothelial Cells/cytology/immunology ; Epitopes/immunology ; Humans ; Immune Tolerance/*immunology ; Immunity, Cellular/*immunology ; Male ; Mice ; Mice, Inbred C57BL ; Sertoli Cells/cytology/*immunology ; Swine ; *Tissue Engineering ; Transplantation, Heterologous