Maturation of antigen-presenting cells is compromised in HLA-G transgenic mice

The human MHC class Ib antigen HLA-G is thought to regulate maternal immune responses during pregnancy. Here we show that expression of HLA-G in trans genic mice diminished cellular immunity by inhibiting maturation of myelomo nocytic cells into functional antigen-presenting cells (APC), Skin allograf ts applied to HLA-G transgenic mice survived longer and resultant T cell re sponses were less potent compared to control mice, T cells from HLA-G mice responded normally to allogeneic APC and immunohistological analyses of spl een revealed no marked abnormalities. However, spontaneous outgrowths of my eloid cells were observed when bone marrow or splenocytes from HLA-G mice w ere cultured in vitro, but functionally competent APC did not develop spont aneously in bone marrow cultures supplemented with granulocyte macrophage c olony stimulating factor (GM-CSF). Addition of lipopolysaccharide (LPS) to GM-CSF-derived bone marrow cultures rescued APC maturation. Studies using H LA-G tetrameric reagents revealed that HLA-G-specific binding activity was associated with CD11c(+) myelomonocytic cells, while binding to lymphoid an d NK cell subsets was undetectable, These data show that spontaneous matura tion of functionally competent dendritic cells IDC) is compromised in HLA-G mice. We hypothesize that HLA-G inhibits maturation of DC via receptor-med iated interactions with myelomonocytic precursors, which render immature DC precursors unable to receive signals from activated T cells.