Expression of class II-MHC antigens in the dermis of patients with progressive systemic sclerosis.
Expression of class II major histocompatibility complex (MHC) antigens on normally negative cell types may convert them into effective antigen-presenting cells. It was therefore of special interest to elucidate whether the main cell populations involved in progressive systemic sclerosis (PSS) express class II antigens on their surfaces and participate in the initiation and/or perpetuation of a cellular immune response in the connective tissue. Immunofluorescence studies on frozen skin sections of scleroderma patients using double-staining techniques revealed a pronounced dermal mononuclear cellular infiltrate with signs of activation manifested by expression of MHC class II antigens in the acute phase of the disease. Most endothelial cells of the papillary and deeper dermal vessels were class II-positive as seen in other inflammatory dermatoses. Moreover, class II antigen-positive fibroblasts were found, especially in the deeper dermis within infiltrated areas around blood vessels. MHC class II molecules were also detected in higher density and on increased numbers of perivascular dermal dendrocytes. On all cell types, HLA-DP was much less frequently expressed than HLA-DR, but more frequent than HLA-DQ. However, in the chronic phase of the disease, with reduced inflammation and increasing sclerosis, MHC class II antigen expression on dermal fibroblasts was again diminished or even absent, as seen in normal and non-PSS inflammatory control biopsies and clinically unaffected skin of scleroderma patients in the acute inflammatory disease stage. Our data speak against a primary expression of class II molecules on PSS-fibroblasts. It seems more likely that Ia-antigens on fibroblasts and an increase of MHC class II positive dermal dendrocytes are induced in an early stage of the disease, i.e., after the influx of the mononuclear infiltrate, most probably by mediators released from these cells. Since an enhanced transcription rate of collagen genes in fibroblasts surrounded by infiltrating cells has been described, this early expression of class II MHC antigens does not seem to play a central role in the induction phase, but rather, may be important in the perpetuation of fibrotic processes in scleroderma.
Gruschwitz
M
M
Institute for General and Experimental Pathology, University of Innsbruck, Austria.
Sepp
N
N
Kofler
H
H
Wick
G
G
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood; D000328:Adult; D000368:Aged; D003713:Dendritic Cells / Q000276:immunology; D004727:Endothelium / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D005434:Flow Cytometry; D006682:HLA-DP Antigens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000276:immunology*; D012867:Skin / Q000276:immunology* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013997:Time Factors
D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D015088:2',5'-Oligoadenylate Synthetase