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 IL-7 blocks SOCS-3 in T cells, allowing them to proliferate and attack the virus-infected cells. (Image: WEHI)
Chronicviral infections can sometimes overwhelm the immune system, leading toa phenomenon some call "immune exhaustion." When this happens, theimmune system is no longer able to fight back effectively against theinfection. Now researchers led by Dr MarcPellegrini from the Walter and Eliza Hall Institute in Melbourne haveshown that boosting the immune system in mice can rid them of a chronicinfection by an HIV-like virus. The findingopens up the possibility of using this immune boosting technique tocombat chronic infections like HIV, hepatitis and tuberculosis. The researchers set out to investigate the mechanisms responsible for immune exhaustion, and to see if they might be reversed. Itwas believed that some system was acting to suppress the immune systemin cases of chronic infection in order to prevent the immune systemoverreacting and possibly damaging other tissue. Theyhypothesised that a cell signalling hormone called interleukin-7(IL-7), which is known for overcoming inhibitory mechanisms, might beable to prevent this suppression of the immune system. Theinfected mice with a virus, Lymphocytic chorimeningitis virus (LCMV)variant clone 13, which establishes a chronic infection similar to thatproduced by HIV. They then injected the micewith human IL-7 and found the mice experienced a "profound" boost toimmune response and were able to eliminate the infection entirely. Themice experienced increased thymic output and saw an increase in T cellnumbers, both T cells that targeted LCMV and other types of T cells aswell. According to Pellegrini, the mechanism atwork behind the scenes was that IL-7 was able to downregulate anotherprotein, SOCS-3, in T cells. It was SOCS-3that was putting the breaks on the immune system in cases of chronicinfection and preventing the body from potentially attacking itself. “Inan overwhelming infection, SOCS-3 becomes highly activated andsuppresses the immune response, probably as a natural precaution toprevent ‘out-of-control’ responses that cause collateral damage to bodytissue,” said Pellegrini. “In the case ofthese overwhelming infections, the immune system effectively slams onthe brakes too early, and the infection persists.” Bydownregulating Soc3, the immune system was able to bounce back andclear the infection, although not without some collateral damage toother tissue caused by the highly active immune system. “Thekey for us was figuring out that turning off SOCS-3 only really workedwhen it was within T cells,” said Simon Preston, a co-author on thepaper. “It allowed the immune response toboost the number of virus-specific T cells and have an immune responsegood enough to eliminate the virus without initiating an immuneresponse that was too large and would make the animal sick.” Thisfinding could have tremendous significance in the field of combatingchronic infection, and could lead to new therapies that might even leadto a cure for HIV. “The findings could help todevelop drugs that target some of these host molecules, such as SOCS-3,and turn them off for very short, defined periods of time toreinvigorate the T cells, allowing them to regroup to fight infection,”said Pellegrini. The researchers suggest thatIL-7 treatment might produce a potent antiviral response while thepatient is undergoing antiretroviral treatment to reduce the viralload. In this situation, it's possible the body might be able toeradicate the infection. The study was published in the journal, Cell,and was supported by the National Health and Medical Research Council,the Canadian Institute for Health and the Cancer Research Institute.
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楼主: StephenW
发表于 2011-2-5 00:36
