Modulation of desmoglein-3-specific T cell response and pathogenic antibody generation in mice.
Pemphigus is a severe blistering disease of the skin and mucous membranes caused by pathogenic autoantibodies to desmosomal adhesion proteins desmoglein-3 (Dsg3) and desmoglein-1 (Dsg1). The antibody titer and the distinct isotype patterns correlated with the disease activity. To identify their functional properties and pathogenic potential, we immunized C57BL/6 and Balb/c mice with recombinant Dsg3 fusion protein plus complete Freund's adjuvant (CFA) or Aluminum Hydroxide hydrate (Alum). After immunization, the cytokine profiles on T cells, the antibody titers, and the isotypes were analyzed. The pathogenicity of different autoantibody isotypes was evaluated by antibody passive transfer approach. It was found that Th1 type cytokine interferon gamma (IFN gamma) was elevated in the CFA-treated group, while Th2 type cytokine interleukin-4 (IL-4) was increased in the Alum-treated group. IgG1 expression was persistent in the Alum group while IgG2a was predominant in the CFA group. Neonatal mice transferred with sera from the Alum group, but not the CFA group, developed skin lesions clinically and histologically with IgG deposition on the epidermal keratinocytes. Our findings suggest that distinct T cell responses could be switched after active immunization combined with different adjuvants, resulting in distinct anti-Dsg3 antibody isotypes with different pathogenic activities in disease development. These findings shed new light on the immunopathogenesis of PV and offer a new therapeutic strategy for this potentially fatal disorder.
Pan
Meng
M
Department of Dermatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Rui Jin Er Road, Shanghai 200025, China.
Zhou
Yun
Y
Li
Weiping
W
Zheng
Jie
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000917:Antibody Formation / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D051184:Desmoglein 3 / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D005786:Gene Expression Regulation; D007106:Immune Sera / Q000276:immunology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010392:Pemphigus / Q000276:immunology*; D011247:Pregnancy; D011485:Protein Binding; D011994:Recombinant Proteins / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D001323:Autoantibodies; D016207:Cytokines; D051184:Desmoglein 3; C495300:Dsg3 protein, mouse; D007106:Immune Sera; D011994:Recombinant Proteins; C041524:aluminum sulfate; D005620:Freund's Adjuvant