Because B-cell activation and antibody production classically necessitate the involvement of CD4+ T cells, Dsg-reactive T cells were capable of recognizing multiple epitopes of the extracellular domain of Dsg and helping B cells to produce a specific antibody. Dsg3-reactive T-cell clones were able to commit polyclonal naive B cells to produce pathogenic anti-Dsg3 antibody and induce the PV phenotype. (Hertl . et al., 1998) Follicular T helper cells (Tfh) are a recently discovered group of CD4+ Th cells with intrinsic differences from Th1, Th2 and Th17 cells. Localized in B-cell follicles of secondary lymphoid tissues, The major function of Tfh cells appears to help B-cell activation and antibody production during humoral immune responses. The Tfh cells express high levels of IL-21, which was demonstrated to be important for the generation of Tfh cells and that responsiveness of Tfh cells to IL-21 drives the formation of the autoimmune reaction, and it clearly impacted on the amount of antibody production.( Gomez. et al.,2011 ; Vogelzang . et al.,2008) Nowadays, finding a promising treatment for pemphigus remains a serious challenge. Various treatments are currently recommended to treat this disease, but they rarely lead to complete and durable remission. Regulatory cells appear to have a critical role in numerous autoimmune diseases, so it is possible that control of these cells may induce remission. (Cholera and Chainani .,2016)