Ventana Medical Systems, Inc. Perforin 760-4394

Perforin is a pore-forming protein that leads to osmotic lysis of the target cells and subsequently enables granzymes to enter the target cells and activate apoptosis, the cell death program. The expression of perforin is upregulated in activated CD8+ T cells, but in NK cells the expression is constitutively very high and stable. Perforin expression can also be stimulated in some activated CD4+ T cells. CD8+ T cells and NK cells use both the perforin / granzyme and the Fas / FasL pathways, while CD4+ T cells preferentially use the Fas / FasL pathway. Although some investigators report a cytolytic potential of CD4+ T cells, it appears more likely that CD8+ T cells are the major effector population in Th1- associated inflammatory skin diseases. The role of perforin-mediated cytotoxicity has been demonstrated in various autoimmune diseases. In vitro and in vivo studies suggest that the cytotoxicity of CTLs maybe mediated by cytotoxic granules in certain inflammatory diseases in humans. In addition, it seems that T-cell cytotoxicity against keratinocytes is mediated by perforin in some inflammatory skin diseases. Other authors suggest that perforin may have a dual role in alloimmune response (organ transplant applications). In one regard, it has a cytolytic function in acute rejection, and, in contrast, it may be responsible for downregulating both CD4- and CD8-mediated alloimmune response.