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Second pathway behind HIV-associated immune system dysfunction identified
Date:9/30/2007

Researchers at the Partners AIDS Research Center at Massachusetts General Hospital (PARC-MGH) may have discovered a second molecular switch responsible for turning off the immune systems response against HIV. Last year members of the same team identified a molecule called PD-1 that suppresses the activity of HIV-specific CD8 T cells that should destroy virus-infected cells. Now the researchers describe how a regulatory protein called CTLA-4 inhibits the action of HIV-specific CD4 T cells that control the overall response against the virus. The report will appear in the journal Nature Immunology and is receiving early online release.

Weve shown that a known regulator of the immune system, CTLA-4, is present in elevated levels on the virus-specific CD4 cells that should be managing the bodys response against HIV, says Daniel Kaufmann, MD, of PARC and the MGH Infectious Disease Unit, a co-first author of the paper. We also found that CTLA-4 expression rises as HIV infection progresses and that the molecule switches off CD4 cell function in a way that appears to be reversible.

Expression of the CTLA-4 protein is known to be elevated on activated T cells, those that have encountered a pathogen and are multiplying rapidly to mount an immune response. Studies in cancer patients have shown that the molecule serves to dampen the immune response, and some preliminary investigations in animals and humans have suggested a potential role in HIV infection. The current study was designed to examine how CTLA-4 may be involved in the dysfunction of HIV-specific T cells that leads to the immune-system breakdown of AIDS.

The researchers first found that CTLA-4 was overexpressed on the HIV-specific CD4 T cells of infected individuals who had not yet received antiviral treatment. Levels were highest in those with symptoms of acute infection and second highest in chronically infected participants. CTLA-4 expression was lowest among a group of parti
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

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