Effect of CD200 and CD200R1 expression within tissue grafts on increased graft survival in allogeneic recipients

In transgenic mice over-expressing CD200 (CD200(tg)) graft survival is associated with increased intragraft expression of mRNAs for genes associated with altered T cell subset differentiation (Foxp3; TGF beta; IL-10). Grafts are rejected in recipients lacking the inhibitory receptor for CD200, CD200R1. We compared grafts of C57BL/6 skin taken from control, CD200KO, CD200(tg), CD200R1KO or CD200(tg).CD200R1KO C57BL/6 donor mice transplanted to control or CD200(tg) BALB/c recipients. Animals received either low-dose rapamycin (0.5 mg/kg), which only enhanced survival in CD200(tg) mice, or high dose rapamycin (1.5 mg/kg) which increased graft survival in all recipients. Recipient draining lymph nodes (DLNs) were analyzed at 14 days post grafting in mixed leukocyte cultures (MLCs) with irradiated BL/6 or C3H/HeJ stimulator cells, assaying antigen-specific cm at day 5. MLC responses were correlated with changes in mRNA gene expression in skin tissue harvested from the same recipients, focusing on genes altered in graft-accepting CD200(tg) recipients. Tissue histology was used to assess graft infiltrating Foxp3(+) Tregs, mast cells (MCs) and their degranulation. CD200(tg) grafts were accepted in control but not CD200KO/CD200R1KO recipients, along with decreased degranulation in graft MCs, diminished DLN MLC responses, and augmented intragraft Foxp3, TGF beta, IL-10 and mast cell gene expression. Skin grafts from either CD200KO or CD200R1KO donors to control mice were rejected, with no change in DLN MLC responses, no altered graft gene expression from that seen using control skin grafts, and pronounced graft MC degranulation. Our data highlight a role for both graft and host CD200/CD200R expression in increased allograft survival. (C) 2012 Elsevier B.V. All rights reserved.