Identification of a novel immunosuppressive DC subpopulation in tolerized heart allografts (145.23)

Abstract

Abstract The role of dendritic cells (DC) in the maintenance of allograft tolerance is unclear. We analyzed the composition and function of DC infiltrates in tolerized murine heart allografts. Methods. B6 donor splenocytes (Day -7) plus anti-CD4 antibody (Day -1, 2 5 and 7) were injected into BALB/c recipients of B6 heart allografts; mice with heart grafts beating > 80 days were considered tolerant. Syngenic heart grafts (B6 to B6) were used as control. Results: We found that graft-infiltrating Lin-CD11c+MHCII+ cDC contained a novel Gr-1+ cDC subpopulation. B220+CD11c+MHCII+ plasmacytoid DC (pDC) were undetectable. In contrast to allograft Gr-1- cDC, which resemble typical immature tissue cDC, Gr-1+ cDC express lower levels of MHC class II and CD11c, adhere to culture plates, exhibit resistance to maturation stimuli, and stimulate allogeneic lymphocytes poorly. Gr-1+ cDC are distributed uniquely in tolerant allografts but not syngenic grafts or acutely rejecting allografts. Gr-1+cDC are absent in lymphoid tissues. Our previous studies have shown that the cytokine milieu of tumors skews pre-cDC differentiation towards Gr-1+ cDC. We found that pre-cDC exist in heart allografts. It remains to be determined whether tolerized hearts promote pre-cDC to differentiate into Gr-1+ cDC in situ. Conclusion: Tolerized allografts contain an immunosuppressive DC subpopulation that may contribute to the maintenance of long-term allograft survival.