IFN-γ-induced iNOS expression in regulatory macrophages prolongs allograft graft survival in fully immunocompetent recipients.. Mus musculus

Mouse monocytes exposed to M-CSF and IFN-γ were driven to a suppressor phenotype over a seven day culture period. The resulting regulatory macrophages (M regs) expressed markers distinguishing them from M0-, M1-, and M2-polarised macrophages and monocyte-derived DCs. M regs completely suppressed polyclonal T cell proliferation through an inducibile nitric oxide synthase (iNOS)-dependent mechanism. Additionally, M regs were found to eliminate cocultured T cells in an allospecific fashion. In a heterotopic heart transplant model, a single intravenous administration of 5x10^6 donor-strain M regs prior to transplantation significantly prolonged allograft survival in fully immunocompetent recipients using both the stringent C3H-to-BALB/c and C57BL/6-to-BALB/c strain combinations; this graft-protective effect was alloantigen-specific. M regs from Nos2-deficient mice did not prolong allograft survival, proving that M reg function in vivo is iNOS-mediated and dependent on living cells. Co-treatment with 1 mg/kg/day rapamycin for 10 days post-transplant markedly enhanced the effect of M regs. In untransplanted C57BL/6 recipients, M regs of BALB/c origin were detectable for up to 2 weeks post-infusion. It is concluded that mouse M regs represent a novel, phenotypically distinct subset of tolerogenic macrophages, which resemble human M regs in their derivation, phenotype and in vitro functions. Overall design: The dataset comprises 36 samples divided into twelve sample groups each representing a certain monocyte/macrophage subtype