Prevention Of Murine Acute Graft-Versus-Host Disease By Recipient-Derived Paired Immunoglobulin-Like Receptor B Lentivirus-Transfected Dendritic Cells

Direct interaction between T-suppressor and dendritic cells (DCs) results in DC tolerance by inducing upregulation of immunoglobulin-like transcript (ILT) 3 and ILT4. DCs were treated with a lentiviral vector containing paired immunoglobulin-like B gene (PIR-B) DCs and the effect of PIR-B-DCs on graft-versus-host disease (GVHD) was analyzed after allogeneic bone marrow (BM) transplantation (BMT). Therefore, 1 x 10(6) recipient-derived PIR-B-DCs were injected into BALB/c (H-2k(d)) mice using BM-splenocyte grafts from major histocompatibility complex-disparate C57BL/6 (H-2k(b)). Our results showed that PIR-B-DCs deficient in surface costimulatory molecules had higher PIR-B protein expression than immature DCs and interleukin 10-treated DCs. Survival analysis showed PIR-B-DC cotransplantation resulted in significant prolongation of allograft survival (mean survival time: 46.0 +/- 13.6 vs. 17.4 +/- 3.6 days in untreated MST; p < 0.01). Furthermore, samples from the liver and skin of a mouse did not show clinical or histological signs of GVHD following the injection of PIR-B-DCs. These results demonstrated that PIR-B-DC cotransplantation may attenuate the severity of GVHD after BMT. Copyright (C) 2010 S. Karger AG, Basel