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International Immunology, Vol. 13, No. 3, 385-394, March 2001
© 2001 Japanese Society for Immunology

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

Anatolij Horuzsko, Francoise Lenfant2,, David H. Munn1, and Andrew L. Mellor

Program in Molecular Immunology, Departments of Medicine and
1 Pediatrics, Medical College of Georgia, Augusta, GA 30912, USA
2 Unite INSERM U395, CHU Purpan, BP 3028, 31024 Toulouse Cedex 3, France

Correspondence to: A. L. Mellor, Program in Molecular Immunology, Medical College of Georgia, 1120 15th Street, CA 2006, Augusta, GA 30912, USA

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 transgenic mice diminished cellular immunity by inhibiting maturation of myelomonocytic cells into functional antigen-presenting cells (APC). Skin allografts applied to HLA-G transgenic mice survived longer and resultant T cell responses were less potent compared to control mice. T cells from HLA-G mice responded normally to allogeneic APC and immunohistological analyses of spleen revealed no marked abnormalities. However, spontaneous outgrowths of myeloid cells were observed when bone marrow or splenocytes from HLA-G mice were cultured in vitro, but functionally competent APC did not develop spontaneously in bone marrow cultures supplemented with granulocyte macrophage colony stimulating factor (GM-CSF). Addition of lipopolysaccharide (LPS) to GM-CSF-derived bone marrow cultures rescued APC maturation. Studies using HLA-G tetrameric reagents revealed that HLA-G-specific binding activity was associated with CD11c+ myelomonocytic cells, while binding to lymphoid and NK cell subsets was undetectable. These data show that spontaneous maturation of functionally competent dendritic cells (DC) is compromised in HLA-G mice. We hypothesize that HLA-G inhibits maturation of DC via receptor-mediated interactions with myelomonocytic precursors, which render immature DC precursors unable to receive signals from activated T cells.

Keywords: dendritic cells, HLA-G, mice, T cells

Transmitting editor: E. Simpson


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