(a) Representative fluorescence activated cell sorter (FACS) results of CD4+T cells apoptosis: I. mean standard deviation (s.d.), median = 396versus2592 865%, mean s.d., median = 241%,P< 00001, respectively]. A similar increase was observed in CD8+T cell apoptosis (5467 1549% mean s.d., median = 573versus2107% 74%, mean s.d., median = 20%,P= 00006, respectively). (iii) By neutralizing FasL with monoclonal antiFasL antibodies, we have shown that this induction of apoptosis by killer B cells is usually FasLdependent. (iv) Increased expression of FasL on CD5hiB cells is usually correlated positively with an increased viral load and the presence of antinuclear antibodies 4E1RCat and rheumatoid factor in HCV. This is the first study in which killer B cells have been suggested to play a pathogenic role in HCV. They seem to be involved in HCV's ability to escape efficient immune responses. Keywords:autoimmunity, B cell, viral load == Introduction == Hepatitis C (HC) is the second most common infectious disease worldwide, with 130150 million cases, and 500 000 deaths annually due to cirrhosis or liver malignancy. The efficient host immune reaction against the various hepatitis C computer virus viral proteins determines viral persistence, the extent of infected hepatocytes and the severity of liver inflammation. It has been shown that this persistence of the hepatitis C computer virus (HCV) is usually associated with the increased presence of autoantibodies. Antinuclear Rabbit polyclonal to TRIM3 antibodies (ANA), rheumatoid factor (RF) and anticardiolipin antibodies (aCL) are the most reported autoantibodies in HC patients with a prevalence of positivity in more than 20% among them1. Once primary immunization has occurred, the repeated generation of apoptotic material (during 4E1RCat persistent viral contamination) might efficiently rechallenge the primed immune system. This capacity for immunederived autoamplification is usually 4E1RCat possibly a critical theory underlying systemic autoimmune disorder2. The first line of defence is usually usually the efficient peripheral immune responses against HCV antigens, mainly cytotoxic T cell response and natural killer (NK) cell activity. Both T and NK cells were shown to eliminate HCVinfected cells by overexpressing Fas ligand (FasL) and/or producing granzyme B (GranB). In the early phase of contamination, B cells produce neutralizing antibodies against different computer virus epitopes, mainly against envelope glycoproteins E1 and E23. Most of these antibodies fail to block the entry of the computer virus into host cells, and therefore the role of humoral antiviral responses remains limited. Chronic HCV contamination and its persistence were reported to be the result of impaired NK cell function and insufficient interferon (IFN) production, in addition to increased secretion of interleukin (IL)10, leading to the failure of HCV cleaning. We reported previously that enhanced peripheral T cell apoptosis in chronic HCV contamination was associated with an increased viral load, autoimmunity and liver disease severity4,5. Of the many possible mechanisms by which HCV infection increases the tendency of T cells to undergo apoptosis, worth mentioning are: (1) downregulation of major histocompatibility complex (MHC) class II and B7 molecules on HCVinfected dendritic cells, which attenuates the delivery of costimulation; (2) inhibition of the production of IFN and IL12, leading to an enhanced responsiveness to IL10 modulating effects and downregulation of T helper type 1 (Th1) responses; (3) induction of autoimmune responses due to crossreactions between HCV core proteins and cryptic epitopes on activated T cells; and (4) enhancement of T cell apoptosis by causing G1/S arrest and cmyc upregulation5. In order to facilitate an efficient process of antiviral cytotoxicity, a balance between regulatory T cell (Treg) function and efficient effector T cell function is required. In this respect, Tregexpansion.