apyrase and Lymphopenia

Ischemia-reperfusion injury (IRI) is a major limiting event for successful liver transplantation, and CD4+ T cells and invariant natural killer T (iNKT) cells have been implicated in promoting IRI. We hypothesized that hepatic overexpression of CD39, an ectonucleotidase with antiinflammatory functions, will protect liver grafts after prolonged cold ischemia. CD39-transgenic (CD39tg) and wildtype (WT) mouse livers were transplanted into WT recipients after 18 hours cold storage and pathological analysis was performed 6 hours after transplantation. Serum levels of alanine aminotransferase and interleukin (IL)-6 were significantly reduced in recipients of CD39tg livers compared to recipients of WT livers. Furthermore, less severe histopathological injury was demonstrated in the CD39tg grafts. Immune analysis revealed that CD4+ T cells and iNKT cells were significantly decreased in number in the livers of untreated CD39tg mice. This was associated with a peripheral CD4+ T cell lymphopenia due to defective thymocyte maturation. To assess the relative importance of liver-resident CD4+ T cells and iNKT cells in mediating liver injury following extended cold preservation and transplantation, WT mice depleted of CD4+ T cells or mice genetically deficient in iNKT cells were used as donors. The absence of CD4+ T cells, but not iNKT cells, protected liver grafts from early IRI.. Hepatic CD4+ T cells, but not iNKT cells, play a critical role in early IRI following extended cold preservation in a liver transplant model.

Topics: Alanine Transaminase; Animals; Antigens, CD; Apyrase; CD4-Positive T-Lymphocytes; Disease Models, Animal; Interleukin-6; Killer Cells, Natural; Liver Transplantation; Lymphopenia; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Reperfusion Injury; T-Lymphocytes, Regulatory; Up-Regulation