T-cellular autoimmunity against desmogleins in pemphigus, an autoantibody-mediated bullous disorder of the skin

Pemphigus encompasses a group of life-threatening blistering diseases of the skin in which loss of adhesion between keratinocytes is caused by autoantibodies (Ab) against desmogleins (Dsg) 1 and 3. There is major interest in characterizing autoreactive T cells that are presumably critical for the induction and regulation of Ab production. In a recent study, peripheral Dsg3-reactive T helper (Th) cells from patients with acute onset, chronic active and remittent pemphigus vulgaris (PV) were quantitated by MACS secretion assay. Dsg3-reactive Th2 cells were detected at similar frequencies in all the studied PV patients while the number of autoreactive Th1 cells exceeded those of the Th2 cells in chronic active PV. Noteworthy, healthy carriers of the PV-associated HLA class II alleles, DRβ1*0402 and DQβ1*0503, exhibited exclusively Th1 reactivity against Dsg3. The titers of Dsg3-reactive IgG were directly related to the ratio of autoreactive Th1/Th2 cells. Moreover, T cell recognition of Dsg3 was restricted by these HLA class II alleles. These findings strongly suggest that (1) Dsg3-reactive Th2 cells are restricted to PV, (2) distinct HLA class II alleles are critical for T cell recognition of Dsg3, and (3) Ab production is associated with both, Th1 and Th2 cells.