Analysis of the T cells that are potentially involved in autoantibody production in pemphigus vulgaris.
Pemphigus vulgaris (PV) is a classical example of an antibody-mediated autoimmune disease of the skin. Direct evidence exists that autoantibodies against the desmosomal adhesion molecule, desmoglein 3 (Dsg3), are critical in the pathogenesis of this disease. The transfer of serum IgG antibodies reactive with Dsg3 into newborn mice induces a bullous skin disease resembling PV. Autoreactive T cell responses to Dsg3 may be critical in the pathogenesis of PV because 1) antibody production generally requires T cell help, 2) the involvement of CD4+ T lymphocytes in PV has been suggested by the strong association with distinct HLA class II alleles, and 3) T cell recognition of epitopes of Dsg3 may be crucial for the initiation and perpetuation of the production of Dsg3-specific autoantibodies by B cells. We and others have identified autoreactive T cells recognizing distinct epitopes of the extracellular portion of Dsg3 in PV patients. These autoreactive CD4+ T cells preferentially produced TH2 cytokines such as IL-4, and IL-10. Autoantibodies of the TH2-dependent IgG4 subtype are preferentially seen in active stages of PV disease, while autoantibodies of the TH1-dependent IgG1 subclass are predominant upon remission of PV. Healthy individuals who carried HLA class II alleles similar or identical to those found to be highly prevalent in PV also developed autoreactive T cell responses to Dsg3. Autoreactive T cells from PV patients produced both TH1 and TH2 cytokines; autoreactive T cells from normals produced TH0 cytokines. These observations suggest that Dsg3-specific T cells may provide targets to eventually modulate the T cell-dependent production of pathogenic autoantibodies in PV.
Hertl
M
M
Department of Dermatology, Medical Faculty, University of Aachen, Germany.
Riechers
R
R
D000483:Alleles; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D015820:Cadherins / Q000276:immunology*; D051184:Desmoglein 3; D006801:Humans; D051379:Mice; D010392:Pemphigus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D015820:Cadherins; C071894:DSG3 protein, human; D051184:Desmoglein 3