Long-Term Limb Allograft Survival Using a Short Course of Anti-CD45RB Monoclonal Antibody, LF 15-0195, and Rapamycin in a Mouse Model

Abstract

A short course of anti-CD45RB mAb and LF 15-0195 prolonged limb allograft survival. The addition of rapamycin induced limb allograft tolerance which is associated with the generation of tolerogenic dendritic cells that suppressed T-cell proliferation.

CD8+ T-Cell Depletion and Rapamycin Synergize with Combined Coreceptor/Stimulation Blockade to Induce Robust Limb Allograft Tolerance in Mice

“…Successful protocols of tolerance induction to limb allograft have been reported in rats (19,(20)(21)(22)(23)(24)(25)(26) and very recently in mouse using BALB/c as recipient strain (27) (34)(35)(36). This approach avoids the necessity to create space or niches in recipient bone marrow through total body irradiation or myeloablative drug administration.…”

Depth and breadth of Canadian military, Veteran and family research: The first decade of Canadian Institute for Military and Veteran Health Research Forums

“…27 In the Income Study, 28 Statistics Canada linked release data with tax records for Regular Force CF veterans who released during 1998-2007. Average income decreased after release, then rose and exceeded pre-release average income by the end of the study decade (1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007). Although rates of low income were low, vulnerable subgroups were identified: those who released under age 20, or as recruits, or involuntarily.…”

Mouse Models of Experimental Vascularized Composite Allotransplantation

“…The success rate was 20 out of 23. Sciatic nerve repair was also performed, although no nerve regeneration or functional recovery study was noted in the article [15]. In Sucher's model, both femoral vessels were repaired using the "cuff" technique.…”

“…The dendritic cell system is believed to play a pivotal role in tolerance induction. Zhong et al introduced their tolerogenic protocol in mouse limb transplantation which appeared to involve dendritic cells [15]. In this study, shortterm combined treatment of anti-CD45RB (3 mg/kg/day) and a 15-deoxyspergualin (DSG) analog called LF 15-0195 (LF, 2 mg/kg/day) was given to limb graft recipients, with (triple treatments) or without (double treatments) rapamycin (2 mg/kg/day).…”

“…On the other hand, seven out of 11 grafts from mice receiving triple treatment had indefinite donor-specific tolerance until the endpoint (100 days) of observation, with low-level mixed chimerism (1 -2 %) maintained throughout the observation period. The underlying mechanism of anti-CD45RB/DSG mediated tolerance was not clear, but their data showed an impaired ability of dendritic cells from tolerant recipients to stimulate T cell proliferation, suggesting a role for dendritic cells in tolerance induction [15].…”