Posttransplant nonfunction of canine islets in PVG rats deficient in complement component C6

Area of Science:

• Transplantation immunology
• Complement system biology
• Xenotransplantation research

Background:

• Islet xenografts often fail immediately in non-immunosuppressed recipients, a phenomenon termed primary nonfunction.
• The role of the complement system, specifically the membrane attack complex (MAC), in this process is not fully understood.
• This study investigates the potential involvement of MAC in the primary nonfunction of transplanted xenoislets.

Purpose of the Study:

• To determine the role of the membrane attack complex (MAC) in the primary nonfunction of canine islet xenografts in PVG rats.
• To compare xenograft outcomes in normocomplementemic and complement-deficient rats under varying immunosuppression protocols.

Main Methods:

• Canine islets were transplanted into nonimmunosuppressed and immunosuppressed normocomplementemic and C6-deficient (C6D) rats.
• Immunosuppression was achieved using a combination of cyclosporine, rapamycin, deoxyspergualin, and mycophenolate mofetil.
• Graft function was monitored by serum glucose levels, and tissue sections were analyzed for inflammation and insulin content.

Main Results:

• Primary nonfunction occurred in all nonimmunosuppressed rats, regardless of complement status.
• The incidence of primary nonfunction was lower (10%) in immunosuppressed C6D rats compared to normocomplementemic rats (33%).
• While cell infiltration showed minimal differences, mean functional islet survival was longer in immunosuppressed C6D rats.

Conclusions:

• The membrane attack complex (MAC) does not appear to be a major factor in the primary nonfunction of canine islet xenografts in nonimmunosuppressed PVG rats.
• A reduced incidence of primary nonfunction and extended survival were observed in immunosuppressed C6D rats.
• These findings suggest a potential minor role for MAC in primary nonfunction within heavily immunosuppressed recipients of islet xenografts.