Natural Killer (NK) cell regulation of antiviral T cell responses in the pathogenesis of HIV infection

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Around 40 million people are currently living with HIV around the globe. HIV remains a leading infectious killer in the world having claimed in excess of 36 million lives to date. Infection with HIV targets the immune system and leads to progressive deterioration of people's ability to survey for and fend off infections and some types of cancer. As the virus impairs and destroys the function of immune cells, affected individuals become gradually more immunocompromised. The most advanced stage of HIV infection is AIDS. Although there is no cure for HIV to date, combination therapy with anti-HIV agents called antiretroviral therapy (ART), prevents the virus from multiplying in the body but cannot eradicate it, stalling the destruction of the body's immune cells. Although effective treatment has resulted in obvious health benefits, accumulating toxicity as a result of lifelong therapy and universal access to therapy are remaining concerns. In addition, ongoing activation of the immune system as seen in treated individuals accounts for a significant proportion of non-AIDS health problems and associated deaths. There is therefore a widely acknowledged need for the development of new and innovative treatments to improve current therapies.The main immune cell type fighting the virus, the T cell, is severely impaired and debilitated during chronic infection. In this study we will be investigating the ability of another type of cell called Natural Killer (NK) cell, to kill the beneficial T cells limiting their antiviral potential. Malfunctioning NK cells may also attack healthy T cells, causing chronic disease instead of fighting it.The purpose of this study is to identify the possible NK cell-mediated pathways leading to T cell deletion. We will use blood samples obtained during routine clinical care of patients infected with HIV following informed consent. Blocking these harmful pathways will boost the immune system leading to improved viral control and prevention of chronic disease and complications.