Dendritic cells, the major antigen-presenting cells of the human colonic lamina propria.
Induction of T-cell responses requires the recognition of antigen in association with class II major histocompatibility complex (MHC) antigens on specialized antigen-presenting cells. It was previously demonstrated that dendritic cells were the major antigen-presenting cell in the mouse intestinal lamina propria whilst macrophages were shown to be suppressive. The aim of this study was to compare the antigen-presenting cell activity of human colonic dendritic cells with macrophages. Colonic mucosa was removed from 46 specimens resected for cancer and other non-malignant conditions and lamina propria cell suspensions obtained by EDTA treatment followed by enzymatic digestion. Lamina propria cell suspensions, depleted of macrophages by adherence to insolubilized human immunoglobulin and carbonyl iron phagocytosis, were enriched for dendritic cells by density gradient centrifugation. Yields represented 0.9% (range 0.7-1.4%) of the starting cell number and the degree of enrichment was 30-50%. Immunocytochemistry demonstrated high levels of class II MHC antigen expression, but low levels or absent expression of macrophage and other markers. The ultrastructural features of the low-density cell fraction were typical of dendritic cells with cytoplasmic extensions or veils and the absence of phagocytic vesicles. Populations of cells enriched for macrophages were obtained by harvesting the human immunoglobulin-adherent cells. These cells were > 70% positive for macrophage markers using immunocytochemistry. The ability of lamina propria cells to induce primary T-cell activation was assayed using allogeneic peripheral blood T cells as responders in the mixed leucocyte reaction (MLR). When antigen-presenting activity was assessed using the MLR, the stimulatory activity was present in the dendritic cell-enriched fraction, with little activity present in the macrophage fraction. These data indicate that dendritic cells, not macrophages, are the major cell population capable of generating a mixed leucocyte reaction in the human colonic lamina propria.
Pavli
P
P
Division of Clinical Sciences, John Curtin School of Medical Research, Woden Valley Hospital, Garran, Australia.
Hume
D A
DA
Van De Pol
E
E
Doe
W F
WF
D002448:Cell Adhesion / Q000276:immunology; D003106:Colon / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006681:HLA-D Antigens / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D006681:HLA-D Antigens