Monday, April 16, 2012

Genetically modified immune system fights HIV

HIV is a particularly dangerous virus because it chooses to infect cells that are part of the immune system. Because of that, our defensive systems break down, leaving us unable to recoup from the viral infection. HIV infects so-called T helper lymphocytes, that function by enabling others to destroy infected cells. Although attempts are being made to boost our immune system, for example by letting other cells take over the role as helpers, or boosting other immune mechanisms, the lack of 'killers' that destroy HIV-infected cells remains a problem. Research conducted by the University of California in Los Angeles has shown that genetically engineering blood stem cells can overcome the lack of HIV destroyers. This should help getting rid of an infection and stop AIDS.

T cells
HIV predominantly infects CD4+ T lymphocytes, which are the aforementioned helpers and are essential for a proper immune response. They are required to activate another form of T lymphocytes, described as CD8+. They are the true killers, destroying cells that have become infected with HIV. Their numbers are too low during an infection because they are not properly activated, due to a lack of CD4+ cells. If they do not receive the proper signals, the CD8+ cells will lie dormant, despite an infection raging through the body.

At the University of California in Los Angeles, scientists genetically engineered blood stem cells with a modified a specific form of a receptor that immune cells use for recognizing infected cells. The blood stem cells started to produce modified CD8+ cells that did not require help to carry out the destruction of cells infected with HIV, after being modified with the genetic code required to make the receptor. Apparently, engineering this form of the T cell receptor into blood stem cells is enough to overcome the lack of activation due to low numbers of CD4+ cells. Scientists obtained the right form of the receptor by cloning it from CD8+ cells that were shown to be functional against HIV-infected cells. Allowing the stem cells to make killers containing the clones appeared to be enough to create a functional army against HIV.
An antigen presenting cell 'reveals' the infection to a CD8+ cell. It also needs signals from CD4+ cells before becoming activated (not shown).  A mature cytotoxic T cell is able to kill infected cells. As shown, activating a CD8+ cell is also achieved by sending signals through the T cell receptor (TCR). HIV-infected cells also present themselves in similar ways, revealing the infection and are thereafter selected for destruction.
The study regarding the cellular engineering was published two years ago, and is found among other novel and interesting new therapies that have so far remained highly experimental. However, the genetically engineered production of killer cells has recently been proven effective in a mouse model that simulates a human HIV infection. The scientists found that planting stem cells capable of producing the much-needed genetically modified killers resulted in lower levels of HIV, while levels of CD4+ T lymphocytes increased. It shows the therapy has the desired effect, thereby proving that the lack of functional infection fighters can be corrected.

Showing that viral levels decrease while the number of HIV target cells are going back up is a good sign. It shows that the method does not just work in theory, or on cells cultured in a lab, but also on live animals that simulate the human form of the disease. Therefore, getting the therapy into the clinic has become more likely, though extensive testing is still required before it will be adopted for human treatment. Nevertheless, it is a promising development in the fight against a virus for which we still have not developed a cure. 

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