Human blood stem cells engineered to kill HIV
A proof-of-principle study has demonstrated that it is possible to engineer human blood stem cells into cells that can target and kill HIV-infected cells. The result is the equivalent of a genetic vaccine which is not only good news in the fight against HIV – the process could also be used against a range of chronic viral diseases. In the study researchers from the UCLA AIDS Institute and colleagues took the “killer” T cells that help fight infection, known as CD8 cytotoxic T lymphocytes, from an HIV-infected individual. The researchers then identified the molecule known as the T-cell receptor – the molecule that guides the T cell in recognizing and killing HIV-infected cells. Although these cells are able to destroy HIV-infected cells, they do not exist in enough quantities to clear the virus from the body. So the researchers cloned the receptor and genetically engineered human blood stem cells, then placed the stem cells into human thymus tissue that had been implanted in mice, allowing them to study the reaction in a living organism. The engineered stem cells developed into a large population of mature, multifunctional HIV-specific CD8 cells that could specifically target cells containing HIV proteins. The researchers also found that HIV-specific T-cell receptors have to be matched to an individual in much the same way that an organ is matched to a transplant patient. The next step is to test this strategy in a more advanced model to determine if it would work in the human body, said co-author Jerome A. Zack, UCLA professor of medicine in the division of hematology and oncology and associate director of the UCLA AIDS Institute. And with the results of the study suggesting the strategy could be an effective weapon in the fight against AIDS, the researchers also hope to expand the range of viruses against which this approach could be used.
“We have demonstrated in this proof-of-principle study that this type of approach can be used to engineer the human immune system, particularly the T-cell response, to specifically target HIV-infected cells,” said lead investigator Scott G. Kitchen, assistant professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA and a member of the UCLA AIDS Institute. “These studies lay the foundation for further therapeutic development that involves restoring damaged or defective immune responses toward a variety of viruses that cause chronic disease, or even different types of tumors.” The study, “Engineering Antigen-Specific T Cells from Genetically Modified Human Hematopoietic Stem Cells in Immunodeficient Mice,” was published on Dec. 7 in the online journal PLoS ONE. news from gizmag.com – Human immunodeficiency virus (HIV) is a lentivirus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk. Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells. The four major routes of transmission are unsafe sex, contaminated needles, breast milk, and transmission from an infected mother to her baby at birth (Vertical transmission). Screening of blood products for HIV has largely eliminated transmission through blood transfusions or infected blood products in the developed world. HIV infection in humans is considered pandemic by the World Health Organization (WHO). From its discovery in 1981 to 2006, AIDS killed more than 25 million people. HIV infects about 0.6% of the world’s population.
In 2005 alone, AIDS claimed an estimated 2.4–3.3 million lives, of which more than 570,000 were children. A third of these deaths are occurring in sub-Saharan Africa, retarding economic growth and increasing poverty.According to current estimates, HIV is set to infect 90 million people in Africa, resulting in a minimum estimate of 18 million orphans.Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but routine access to antiretroviral medication is not available in all countries. HIV primarily infects vital cells in the human immune system such as helper T cells (specifically CD4+ T cells), macrophages, and dendritic cells. HIV infection leads to low levels of CD4+ T cells through three main mechanisms: firstly, direct viral killing of infected cells; secondly, increased rates of apoptosis in infected cells; and thirdly, killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections. Most people infected with HIV eventually develop AIDS. These individuals mostly die from opportunistic infections or malignancies associated with the progressive failure of the immune system.HIV progresses to AIDS at a variable rate affected by viral, host, and environmental factors; HIV-specific treatment delays this process. Most will progress to AIDS within 10 years of HIV infection: some will have progressed much sooner, and some will take much longer. Treatment with anti-retrovirals increases the life expectancy of people infected with HIV. Even after HIV has progressed to diagnosable AIDS, the average survival time with antiretroviral therapy was estimated to be more than 5 years as of 2005.Without antiretroviral therapy, someone who has AIDS typically dies within a year.
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