Development and Characterization of Desmoglein-3 Specific T Cells from Patients

Pemphigus vulgaris (PV) is a cutaneous autoimmune dis-ease characterized by blister formation in the suprabasilar layers of skin and mucosae and anti–desmoglein-3 (Dsg3) autoantibodies bound to the surface of lesional keratino-cytes and circulating in the serum of patients. This disease can be reproduced in neonatal mice by passive transfer of patients ’ IgG, indicating that humoral immunity plays an important role in the pathogenesis of PV. Currently, the role of T lymphocytes in the development of PV is not clear. Here, we report that three immunoreactive segments of the ectodomain of Dsg3 specifically induced proliferation of T cells from PV patients. We found that T lymphocytes from 13 out of 14 patients responded to at least one of three Dsg3 peptides. T cells from controls and other patient groups did not respond to these Dsg3 peptides. The major T cell popu-lation stimulated by these Dsg3 peptides was CD4 positive. Dsg3-specific T cell lines and clones were developed and were shown to express a CD4 positive memory T cell pheno-type. Upon stimulation, these cell lines and clones secreted a Th2-like cytokine profile. The Dsg3 responses of these T cells were restricted to HLA-DR, and not-DQ and-DP, of the major histocompatibility complex. This information will help to elucidate the cellular immune abnormalities leading to production of pathogenic IgG autoantibodies in patients with PV.