Chronic graft rejection mediated by cellular immune responses still poses a serious clinical problem in transplant surgery. Chemokines coordinate the recruitment of leukocytes in inflammatory and immune responses. Their precise functions in the rejection of allografts are still ill defined. This study investigates the role of chemokine receptor 4 (CCR4) in acute and chronic cardiac allograft rejection in mice. Allogeneic hearts were transplanted into CCR4 deficient (CCR4 -/-) and control recipients. Reverse transcription-PCR showed transcription of macrophage-derived chemokine and thymus and activation-regulated chemokine, the cognate chemokine ligands of CCR4, within the graft. Compared to wild-type controls, acute allograft rejection in CCR4 -/-recipients was only slightly prolonged. In contrast, in a gallium nitrate chronic cardiac allograft rejection model, cardiac graft survival was significantly prolonged in CCR4 -/-recipients. A relative increase in the percentage of graft infiltrating CD8 + T cells in CCR4 -/-recipients was observed 30 days after transplantation and was accompanied by a decrease in CD4 + T cells. Moreover, the percentage of NK1.1 + CD3 + graft-infiltrating cells was significantly reduced on day 5 and day 30 post transplantation. These findings indicate that CCR4 is involved in the recruitment of NK1.1 + CD3 + cells into cardiac allografts and clearly establish an important and novel role for CCR4 in chronic graft rejection.

Benign and low malignant tumors of the middle pancreatic segment can be resected by extended pancreaticoduodenectomy or distal pancreatic resection. Both procedures involve unavoidably extensive loss of normal pancreatic parenchyma, leading to deteriorated endocrine and exocrine pancreatic function. Segmental pancreatic resection represents an organ-preserving surgical procedure. Normal pancreatic tissue can be preserved as only the tumor with a pancreatic segment is resected. Several reports confirm lower mortality and minimal risk of postoperative endocrine or exocrine insufficiency than with standard pancreatic resections. The indication should be limited exclusively to benign or low malignant pancreatic tumors, metastases from other tumors, and focal chronic pancreatitis, as this type of resection cannot be deemed oncologic. Segmental pancreatic resections are technically more demanding and therefore should be performed in experienced centers.