BACKGROUND: Failure of costimulatory molecule-deficient donor dendritic cells (DCs) to induce indefinite allograft acceptance may be a result of the 'late" up-regulation of these molecules on the DCs after interaction with host T cells. Ligation of @entity14636 on antigen-presenting cells by its cognate ligand @entity4458 is thought to induce expression of @entity8271 (B7-1) and @entity11787 (B7-2). We examined the influence of anti- @entity4458 monoclonal antibody (mAb) on the capacity of donor-derived DC progenitors to induce long-term allograft survival. METHODS: High purity DC progenitors were grown from B10 (H2b) @entity19 bone marrow in granulocyte-macrophage colony-stimulating factor and transforming growth factor beta1 ( @entity641 ). Mature DC were propagated in granulocyte-macrophage colony-stimulating factor and @entity58 . Their phenotype was characterized by flow cytometric analysis and their function by mixed leukocyte reactivity. Anti-donor cytotoxic T lymphocyte activity in grafts and spleens of vascularized heart allograft recipients was also assessed. RESULTS: The @entity11580 -cultured cells were (1) DEC 205-positive, MHC class II-positive, CD80dim, CD86dim, and CD40dim, (2) poor stimulators of naive allogeneic T-cell proliferation, and (3) able to prolong significantly B10 cardiac allograft survival in C3H (H2k) recipients when given (2 x 10[6] i.v.) 7 days before organ transplantation (median survival time [MST] 26 days vs. 12 days in controls, and 5 days in @entity58 DC-treated animals). Their allostimulatory activity was further diminished by addition of anti- @entity4458 mAb at the start of the mixed leukocyte cultures. Anti- @entity4458 mAb alone (250 microg/ @entity19 , i.p.; day -7) did not prolong cardiac graft survival (MST 12 days). In contrast, @entity641 -cultured DCs + anti- @entity4458 mAb extended graft survival to a MST of 77 days, and inhibited substantially the anti-donor cytotoxic T lymphocyte activity of graft-infiltrating cells and host spleen cells assessed 8 days after transplant. CONCLUSIONS: The @entity14636 - @entity4458 pathway appears important in regulation of allogeneic DC-T-cell functional interaction in vivo; its blockade increases markedly the potential of costimulatory molecule-deficient DCs of donor origin to induce long-lasting allograft survival.

Blockade of the XXXX - @entity14636 ligand pathway potentiates the capacity of donor-derived dendritic cell progenitors to induce long-term cardiac allograft survival.

@entity19 :: ('10090', 'Species') :: ['mouse'] @entity8271 :: ('12519(Tax:10090)', 'Gene') :: ['CD80'] @entity641 :: ('21803(Tax:10090)', 'Gene') :: ['TGFbeta1', 'TGFbeta'] @entity14636 :: ('21939(Tax:10090)', 'Gene') :: ['CD40'] @entity11787 :: ('12524(Tax:10090)', 'Gene') :: ['CD86'] @entity4458 :: ('21947(Tax:10090)', 'Gene') :: ['CD40L'] @entity58 :: ('16189(Tax:10090)', 'Gene') :: ['interleukin-4'] @entity11580 :: ('21809(Tax:10090)', 'Gene') :: ['TGFbeta3']
@entity14636 :: (21939(Tax:10090),Gene) :: ['CD40']
