Some people, known as HIV nonprogressors, are able to carry an HIV infection for an apparently indefinite period of time without having it progress into a full blown AIDS infection. As early as the mid-eighties some researchers wondered why that was possible, and in 1986 Dr. Jay Levy of the University of California, San Francisco, proposed a reason. His research indicated that there was a protein produced by CD8 lymphocytes which conferred much greater HIV response strength to the immune system. Accordingly, Levy termed the mystery factor CD8 Antiviral Factor (or CAF); the search for what CAF actually is and how it works has been going on ever since.

CD4 is the type of lymphocyte most often infected by HIV, due to its abundance of CXCR4 and CCR5 coreceptors, which the virus moves through to infect the cell. Some of the nonprogressors were discovered to have neither of these receptors, or mutated versions of them, preventing the virus from killing their CD4 cells. In Levy's research, it was discovered that in other nonprogressors, when CD8 and CD4 cells together were exposed to HIV, the CD4 cells were able to stop replication of the HIV without dying themselves. However, when the CD8 lymphocytes were removed, HIV infection proceeded the same as within a control population -- in other words, there was very good evidence that some factor produced by CD8 was controlling the infection. Further research found that in most cases of HIV, the factor seems to be switched off at some point during the normal progression of HIV, likely just before the time it becomes classifiable as AIDS.

It has become apparent in the past decade that there is probably more than one protein component to CD8, due to conflicting findings in several studies. One possibility was discovered in 1995, at Dr. Robert Gallo's lab at the National Cancer Institute: three chemokines uniquely made by CD8 cells. Chemokines in general act to signal other immune system cells that there is something amiss, and thus begin a systemic reaction to certain pathogens etc. The researchers theorized that the CD8 chemokines caused an immune system response that could hold HIV in check. Initial tests were promising, with HIV reproduction inhibited in the test tube upon introduction of the chemokines, but studies using different strains of HIV sometimes showed little or no inhibition -- CD8 chemokines were apparently not the whole story.

In early September of 2002, Dr. David Ho of the Aaron Diamond AIDS Reserch Center announced new findings that indicate three other proteins, alpha-defensins, as probable antiviral factors. These have been known for a while as antibacterial agents produced by the CD8 lymphocytes, which act to break down bacterial walls much like an artificial antibiotic. The way they affect HIV is currently unknown, though it is either by some action of their own or by causing an external effect somewhere down the line like the chemokines. To test their hypothesis, the researchers did in vitro testing indicating that when defensins are taken away, immune cell susceptibility to HIV jumps way up.

Both of these findings point to possible new treatment vectors, as both make use of factors which the body should produce naturally. Figuring out how to bring the CD8 cells' production of CAF's back online, or strengthen it while it is still going is one approach. Replacing the various CAF components with artificial substitutes is another. Hopefully, within ten years drugs that take advantage of our knowledge of CAF will begin to appear on the international market.

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