Skewed T-cell receptor variable β repertoire and massive T-cell activation in idiopathic orofacial granulomatosis.
Orofacial granulomatosis (OFG) is a clinicopathologic entity describing oral lesions with noncaseating granulomas including a spectrum of diseases such as the Melkersson-Rosenthal syndrome. The involvement of abnormal T-cell responses has been suggested in the pathogenesis of OFG although few and contrasting data are currently available on this issue. In a patient with OFG, we observed virtually complete CD4 and CD8 T-cell receptor (TCR) β-chain variable region (BV) repertoires at the lesion level and in circulation. However, oligoclonal profiles were found in CD4 and, to a greater extent, in CD8 subsets. These findings were seen in association with a massive peripheral T-cell activation, decreased naive T cells, reduced thymic output, altered cytokine production, and increased apoptosis. Our data, pointing to a random influx of T cells at the site of inflammation, argue against the hypothesis of a main allergen acting at the level of oral mucosa. The profound dysregulation of the peripheral T-cell compartment suggests that OFG should be regarded as a systemic disorder with localized manifestations.
A
A
Giovannetti
F
F
Mazzetta
A
A
Cavani
D
D
Pennino
E
E
Caprini
E
E
Ortona
G
G
Donato
E
E
Rosato
F
F
Salsano
M
M
Pierdominici
D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008046:Lip / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008556:Melkersson-Rosenthal Syndrome / Q000175:diagnosis / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
D015415:Biomarkers; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta