Mechanism of Humoral and Cellular Immune Modulation Provided by Porcine Sertoli Cells

Abstract

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.

Xenotransplanted Pig Sertoli Cells Inhibit Both the Alternative and Classical Pathways of Complement-Mediated Cell Lysis While Pig Islets Are Killed

“…MCP and DAF accelerate the degradation of C3 and C5 convertases as well as limit the production of proinflammatory molecules, while clusterin and CD59 inhibit the assembly of the MAC 21 . The mRNA for these inhibitors has been detected in mouse and porcine SCs 15,22,23 and was confirmed by this study. Here we report for the first time that NPSCs express significantly higher levels of clusterin, MCP, and DAF mRNA as well as significantly higher levels of MCP and DAF proteins compared to NPIs.…”

Resistance of neonatal porcine Sertoli cells to human xenoantibody and complement-mediated lysis is associated with low expression of α-Gal and high production of clusterin and CD59

“…and Lee et al. [13,14] demonstrated that NPSCs could inhibit human natural antibody‐mediated lysis by preventing MAC formation, the exact mechanisms were still unknown. In this study, we confirmed their results and identified the possible mechanism of resistance as being related to diminished α‐Gal expression and relatively higher clusterin and CD59 (membrane inhibitor of reactive lysis) as compared with control endothelial cells.…”

Renoprotective Effects of Cotransplanted Allogeneic Testicular Sertoli Cells in a Renal Acute Rejection Model in Rats

“…[4][5][6][7][8][9][10][11][12][13] In cotransplanted with allogeneic cells, Sertoli cells not only are immune privileged, but also assist fibromyoblasts and islet cells in escaping immune rejection, which allows the long-term survival of the grafts. [14][15][16][17][18][19] Such privilege is thought to be associated with the FasL expressed on the surface of Sertoli cells.…”