CD4(+) T cells play an important role in acute experimental pancreatitis in mice

Background & Aims: Few data are available on the potential role of T lympho cytes in experimental acute pancreatitis. The aim of this study was to char acterize their role in the inflammatory cascade of acute pancreatitis. Meth ods: To type this issue, acute pancreatitis was induced by repeated injecti ons of cerulein in nude mice and in vivo CD4(+) or CD8(+) T cell-depleted m ice. The role of T lymphocyte-costimulatory pathways was evaluated using an ti-CD40 ligand or anti-B7-1 and -B7-2 monoclonal blocking antibodies. The r ole of Fas-Fas ligand was explored using Fas ligand-targeted mutant (genera lized lymphoproliferative disease) mice. Severity of acute pancreatitis was assessed by serum hydrolase levels and histology, Intrapancreatic interleu kin 12, interferon gamma, Fas ligand, and CD40 ligand messenger RNA were de tected by reverse-transcription polymerase chain reaction. Intrapancreatic T lymphocytes were identified by immunohistochemistry. Results: In control mice, T cells, most of them CD4(+) T cells, are present in the pancreas and are recruited during acute pancreatitis. In nude mice, histological lesion s and serum hydrolase levels are significantly decreased. T-lymphocyte tran sfer into nude mice partially restores the severity of acute pancreatitis a nd intrapancreatic interferon gamma, interleukin 12, and Fas ligand gene tr anscription. The severity of pancreatitis is also reduced by in vivo CD4(+) (but not CD8(+)) T-cell depletion and in Fas ligand-targeted mutant mice. Blocking CD40-CD40 ligand or B7-CD28 costimulatory pathways has no effect o n the severity of pancreatitis. Conclusions: T lymphocytes, particularly CD 4(+) T cells, play a pivotal role in the development of tissue injury durin g acute experimental pancreatitis in mice.