REVIEWS  PEMPHIGUS 

Giornale Italiano di Dermatologia e Venereologia 2007 August;142(4):353-62

Copyright © 2007 EDIZIONI MINERVA MEDICA

language: English

T cell involvement in pemphigus

Gilbert D. ¹, Mouquet H. ¹, Joly P. ^{1, 2}

¹ INSERM U519, Federate Institute for Multidisciplinary Research on Peptides, Faculty of Medicine and Pharmacology Rouen, France 2 Department of Dermatology Charles Nicolle University Hospital, Rouen, France

Pemphigus are rare organ-specific autoimmune blistering diseases, characterized by pathogenic autoantibodies directed against desmogleins, specific desmosomal transmembrane glycoproteins. Binding of autoantibodies to their targets induces a loss of adhesion between keratinocytes resulting in blister formation. There are many arguments to consider that both induction and regulation of autoantibody production need the activation of specific autoreactive T cells. At first, the major histocompatibility complex, in particular the class II locus was demonstrated to be associated with pemphigus. Subsequently, the activation of autoreactive T cells by the extracellular domain of Dsg1 and Dsg3 was demonstrated in pemphigus foliaceus (PF) and pemphigus vulgaris (PV) patients respectively. The T cell recognition of different Dsg3 peptides was restricted by HLA class II molecules and was also obtained in healthy individuals who carried PV-associated HLA class II alleles. Both Th1 and Th2 T cell clones were detected in PV patients, at different stages of the disease and the ratio Th1/Th2 was shown to be related to the anti-Dsg3 autoantibody titer. Interestingly, healthy subjects exclusively exhibited Th1 reactivity against Dsg3. Furthermore, the presence of Type 1 regulatory cells (Tr1) was mainly found in healthy subjects, suggesting that an imbalance between Th1, Th2 and Tr1 cells may be critical for the tolerance breakdown observed in pemphigus patients.