Direct characterization of human T cells in pemphigus vulgaris reveals elevated autoantigen-specific Th2 activity in association with active disease.
Pemphigus vulgaris (PV) is a blistering skin disorder mediated by autoantibodies targeting the epidermal adhesion molecule desmoglein 3 (Dsg3). As Th2-associated cytokines are necessary for directing antibody production, it is hypothesized that Dsg3-specific Th2 activity is associated with active disease. We used cell-surface-matrix technology in combination with flow cytometry to characterize the Dsg3-reactive T-cell population using peripheral blood mononucleocytes sampled from PV patients stratified by active (n = 9) or remittent disease (n = 6), and healthy human leucocyte antigen-matched controls (n = 5). We evaluated interferon-gamma-producing CD4+ cells (Th1) and interleukin (IL)-10- or IL-4-producing CD4+ cells (Th2). The mean frequency of Th2 CD4+ T cells was significantly elevated for five of nine PV patients with active disease. No significant Th2 responses were detected for patients with remittent disease or controls. There was a significant association of Th2 activity with active disease compared with remittent and control groups (P = 0.026 and P =0.012, respectively), and Th2 activity was significantly correlated with anti-Dsg3 IgG titre (P = 0.044). One patient with remittent disease converted from a Th2-negative to a Th2-positive response with the initiation of disease activity. An antigen-specific CD4- lymphocyte response was detected in five PV patients (36%), and was shown to correlate closely with the CD8+ population. These results are consistent with the hypothesis that Th2 response directs autoantibody production and is therefore associated with disease activity in PV.
Rizzo
C
C
Department of Dermatology, Weill Medical College of Cornell University, New York, NY 10021, USA.
Fotino
M
M
Zhang
Y
Y
Chow
S
S
Spizuoco
A
A
Sinha
A A
AA
D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D051184:Desmoglein 3 / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D010392:Pemphigus / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; C071894:DSG3 protein, human; D051184:Desmoglein 3; D018984:Epitopes, T-Lymphocyte