Galectin-9 in Combination With Rapamycin Induces Cardiac Allograft Tolerance in Mice

• DOI: 10.1097/tp.0b013e31829b07b5
• Publication Date: 2013-07-09T13:52:58Z
• Authors: Lanjun Cai; Hongmin Zhou; Zemin Fang; Jin Yuan; Toshiro Niki; Mitsuomi Hirashima; Wentao He; Zhonghua Klaus Chen
• Keywords: CD80; CD86; Proinflammatory cytokine; Galectin

Galectin-9 serves opposing roles in the innate and adaptive immune systems. triggers T-cell immunoglobulin mucin-3 (Tim-3) on T helper type 1 (Th1) cells, thereby terminating Th1 immunity protecting allografts from host attacks. Meanwhile, galectin-9 promotes maturation of dendritic cells (DCs) that deliver proinflammatory signals. We previously showed significantly prolongs cardiac allograft survival mice but failed to induce tolerance. This study aimed at improving administration protocol examined whether rapamycin can reverse effects DCs synergizes with tolerance.Monocytes/DCs were assessed for Tim-3 expression by flow cytometry. Costimulatory molecules CD80/CD86 measured galectin-9/rapamycin-treated bone marrow-derived performed heterotopic cervical transplantation using BALB/c donors C57BL/6 recipients graft time. long-term surviving immunoassayed interferon-γ interleukin-4 secretion.Allograft-infiltrating monocytes/DCs expressed high levels (47.3%±5.6%). Expression was up-regulated galectin-9-treated DCs, which reversed rapamycin. Combined treatment promoted permanent acceptance fully mismatched grafts (survival time >180 days; n=6). However, or alone not sufficient Galectin-9/rapamycin-induced tolerance associated low donor-specific secretion.Rapamycin inhibits DCs. tolerance, is reduced Th2 responses.