Of course, the “virus” is “self” under those conditions, meaning that the immune system doesn’t react to it. So Chisari’s group immunized other mice to raise HBV-specific CTL, and transferred the CTL into the transgenic mice.3 These HBV-specific CTL did two things: They apparently controlled the virus “infection”, and they damaged the liver.4 The presumption was that the two findings were the same effect, and the CTL were trying to eliminate virus by killing liver cells: “Our data show that antigen-specific immune effector mechanisms can destroy HBV-positive hepatocytes in vitro and in vivo … “.
Hepatitis viruses
Six years later, though, they were suggesting the opposite, demonstrating that in fact CTL were controlling the “virus” through a non-cytolytic mechanism.5 (Actually, they showed very similar data a couple of years earlier than that,6 but the 1996 paper went further with the mechanisms and was overall more solid.) Essentially, they demonstrated that CTL were shutting down virus expression in the liver by releasing interferon and other cytokines. There is some liver damage, but it’s not necessarily because of direct cytotoxity; it’s a side-effect of the cytokines, not directly related to the viral clearance. (Recently, it’s been proposed that the CTL make a decision which route to go — cytotoxicity vs. cytokine-mediated control — based on the amount of virus antigen. 7 This might offer a way to manipulate this and drive the response to the most effective system in other infections, though it’s far from trivial to adjust amount of viral antigen.)
Hepatitis viruses
Six years later, though, they were suggesting the opposite, demonstrating that in fact CTL were controlling the “virus” through a non-cytolytic mechanism.5 (Actually, they showed very similar data a couple of years earlier than that,6 but the 1996 paper went further with the mechanisms and was overall more solid.) Essentially, they demonstrated that CTL were shutting down virus expression in the liver by releasing interferon and other cytokines. There is some liver damage, but it’s not necessarily because of direct cytotoxity; it’s a side-effect of the cytokines, not directly related to the viral clearance. (Recently, it’s been proposed that the CTL make a decision which route to go — cytotoxicity vs. cytokine-mediated control — based on the amount of virus antigen. 7 This might offer a way to manipulate this and drive the response to the most effective system in other infections, though it’s far from trivial to adjust amount of viral antigen.)
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