Healthy human immune system cells can respond to HIV-1
Findings offer hope for vaccine against AIDSAIDS patients' failure to clear HIV-1 might not be due to the inability of the human immune system to recognise the virus, as was previously thought. A study published today in the open access journal Medical Immunology shows that cultured immune system cells taken from healthy individuals recognise and respond to HIV-1 proteins. Cells taken from infected individuals, however, are much less responsive to the virus. These findings need to be reproduced in vivo, but they do offer new hope for a vaccine against AIDS. Exposing healthy individuals to HIV-1 proteins before they are infected with the virus might train their immune system to respond to the virus and prevent them from developing AIDS.
The study was conducted by Pedro Reche and Derin Keskin from the Dana-Farber Cancer Institute, Boston, USA and other colleagues from Dana-Farber and Harvard Medical School, Boston, USA. They used bioinformatics techniques to predict which HIV-1 protein fragments – or 'epitopes' - were likely to trigger a response from immune system cells called cytotoxic T lymphocytes. They identified 37 epitopes. Reche, Keskin et al. then predicted which of these 37 epitopes were likely to be recognised by most people's immune systems, taking into account genetic differences in immune system genes, called HLA genes, depending on ethnic origin. They identified 25 epitopes, which they combined into five pools with which to test immune responses. They predicted that only 5 of these epitopes would be recognised by over 95% of people's immune systems.
The authors exposed cultured lymphocytes from HIV-1 infected patients to the epitope pools, and repeated the experiment with cultured lymphocytes from healthy donors. They assessed the response to the epitopes by measuring the levels of interferon gamma (IFN gamma) produced by the cultured T lymphocytes – IFN gamma is produced by responsive T lymphocytes upon activation by pathogenic or viral proteins and helps to destroy infectious organisms.
Reche, Keskin et al.' s results show that only a small proportion of cells from HIV-1infected patients recognised the epitopes and mounted an adequate immune response: cells from only 31-45% of patients produced IFN gamma, and in small quantities. By contrast, cells from all healthy donors responded and produced IFN gamma in large quantities. The authors also demonstrate that these exposed lymphocytes from uninfected individuals could kill HIV-1 infected cells.
Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes
Pedro A Reche, Derin B Keskin, Rebecca E Hussey, Petronela Ancuta, Dana Gabuzda and Ellis L Reinherz
Medical Immunology 2006, (in press)
After the embargo, article available from the journal website at: http://www.medimmunol.com/
This article is accompanied by an editorial available from the journal website after the embargo
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