A subset of human dendritic cells in the T cell area of mucosa-associated lymphoid tissue with a high potential to produce TNF-alpha.
Recently, a new class of human dendritic cell (DC) precursors has been described in the peripheral blood recognized by the mAb M-DC8. These cells represent approximately 1% of PBMC and acquire several characteristics of myeloid DC upon in vitro culture. In this report we show that M-DC8(+) monocytes secrete in response to LPS >10 times the amount of TNF-alpha as M-DC8(-) monocytes, but produce significantly less IL-10. Consistent with a role in inflammatory responses, we found that M-DC8(+) cells localized in the T cell area of inflamed human tonsils and in the subepithelial dome region of Peyer's patches. In patients with active Crohn's disease, abundant M-DC8(+) cells were detectable in inflamed ileal mucosa, which were entirely depleted after systemic steroid treatment. Our results indicate that M-DC8(+) cells are cells of DC phenotype in inflamed mucosa-associated lymphoid tissue that may contribute to the high level of TNF-alpha production in Crohn's disease. We infer that selective elimination of M-DC8(+) cells in inflammatory diseases has therapeutic potential.
de Baey
Annegret
A
Micromet AG, Munich, Germany. debaey@tvmvc.de
Mende
Ines
I
Baretton
Gustavo
G
Greiner
Axel
A
Hartl
Wolfgang H
WH
Baeuerle
Patrick A
PA
Diepolder
Helmut M
HM
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D014066:Palatine Tonsil / Q000276:immunology / Q000473:pathology; D010581:Peyer's Patches / Q000276:immunology / Q000473:pathology; D011241:Prednisone / Q000627:therapeutic use; D018805:Sepsis / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D011241:Prednisone