Localized Wegener's granulomatosis: predominance of CD26 and IFN-gamma expression.
The immune response in Wegener's granulomatosis (WG) has been characterized as a predominant, potentially pathogenic Th1-like reaction by blood T cells and T-cell clones from diseased tissues. To elucidate further the immunopathogenic mechanisms, this study analysed the phenotypes of inflammatory infiltrates in frozen nasal biopsies with involvement of the upper respiratory tract only (localized or 'initial phase' WG) and with multi-organ involvement, including systemic vasculitis (generalized WG). The expression and production of Th1 and Th2 cytokines were examined in tissue specimens and peripheral blood mononuclear cells (PBMCs) of localized and generalized WG. The number of CD3+ T cells in inflammatory infiltrates ranged from 50 to 70%, together with approximately 30% CD14+ monocytes/macrophages. An average of 40% of T cells expressed CD26 in nasal biopsies of localized WG, compared with about 16% in specimens of generalized WG. In parallel, a higher number of interferon-gamma (IFN-gamma)-positive cells were detected in nasal tissue of localized than in generalized WG. PBMCs from localized WG similarly exhibited higher spontaneous IFN-gamma production in contrast to generalized WG (207 vs. 3 pg/ml, p<0.05). Interleukin-4 (IL-4) mRNA was found in higher amounts in generalized than in localized WG. IL-4 production was negligible in both disease and controls. In addition, both IL-10 mRNA and IL-10 protein levels of activated PBMCs from localized WG were elevated when compared with generalized disease (574 vs. 154 pg/ml, p<0.05) or healthy controls (574 vs. 246 pg/ml, p<0.05). It is conluded that in nasal tissues, mainly CD4+/CD26+ T cells as well as IFN-gamma-positive cells may support a polarized Th1-like immune response. Furthermore, the data suggest that this in situ immune response is already initiated and established in localized WG, accompanied by increased peripheral IFN-gamma and IL-10 production.
Müller
A
A
Department of Rheumatology and Rheumaklinik Bad Bramstedt, Medical University of Lübeck, Lübeck, Germany. mueller@medinf.mu-luebeck.de
Trabandt
A
A
Gloeckner-Hofmann
K
K
Seitzer
U
U
Csernok
E
E
Schönermarck
U
U
Feller
A C
AC
Gross
W L
WL
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D018929:Cell Culture Techniques; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D014890:Granulomatosis with Polyangiitis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D018819:Dipeptidyl Peptidase 4