Cognate Th2-B cell interaction is essential for the autoantibody production in pemphigus vulgaris.
Pemphigus vulgaris (PV) is a Th2-dominant autoimmune skin disease. We showed that indeed active PV patients had a biased Th2 response and specific IgG4 autoantibodies were dominant. To further investigate the role of antigen-specific Th2 cells in the regulation of pathogenic Dsg3-IgG antibody production, we used recombined Dsg3 protein to immunize wild-type C57BL/6 mice with aluminum hydroxide or complete Freund's adjuvant as adjuvant. CD4(+) T cells from Dsg3-immunized mice were adoptively transferred into TCR-β chain deficient mice. The transferred CD4(+) T cells were readily seen in the peripheral blood and spleen, and interacted with B cells, resulting in B-cell activation. Furthermore, transferred CD4(+) T cells from mice immunized with Dsg3 plus Alum with Th2 phenotype were able to render unprimed B cells to secrete Dsg3-specific IgG1 antibody in vivo. Taken together, these results provide the first demonstration of direct role of Dsg3-reactive CD4(+) T (Th2) cells in the regulation of pathologic anti-Dsg3 antibody production.
Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Rui Jin Er Road, Shanghai, China.
Haiqin
H
Zhu
Yayuan
Y
Chen
Yun
Y
Zhou
Ying
Y
Wang
Jie
J
Zheng
Meng
M
Pan
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D051184:Desmoglein 3 / Q000276:immunology; D051182:Desmogleins / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010392:Pemphigus / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D051184:Desmoglein 3; D051182:Desmogleins; D007074:Immunoglobulin G