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The strongest cytotoxic responses generally occur just after plasma viral levels peak, usually around 12 weeks after initial infection (Paul, 2003), but their activity throughout the infection is crucial to the level of progression of the virus. Long-term non-progressors have high quantities of HIV-1-specific CTL precursors, but can occasionally develop so-called "escape mutants" that allow the virus to rapidly destroy CD4+ cells after several years of relative inactivity (Rubbert et al, 2006). Variations in HLA alleles plays a role in an individuals ability to mount a cellular response to HIV; certain HLA phenotypes are better to activate CD8 T cells when couples with HIV-antigen than other phenotypes are (Rubbert et al, 2006). Specifically, HLA B14, B27, B51, B57 and C8 seem to offer some advantage for activating a cellular response to the virus, and interestingly, heterosexual couple with different HLA-1 alleles have some protective immunity towards transmission of HIV (Rubbert et al, 2006).
There is evidence that cellular response can be primed in effect by an exposure to HIV when infection does not occur. Some non-infected heterosexual partners of HIV+ individuals have been found to have Nef-specific cytotoxic responses, and similar findings have come from individuals exposed to the virus through needle-sticks (Rubbert et al, 2006). Beyond the standard cytotoxic response to the virus, CD8+ T cells have been shown to have antiviral activity even without direct cell-cell contact: MIP-1alpha, MIP-1beta and RANTES (chemokines released by the CD8+ cells) serve as ligands for CCR5. By binding to CCR5, a co-receptor for HIV-1, the chemokines inhibit the viruses ability to enter the cell. CAFs, or CD8+ T-cell antiviral factors are able to help curb viral replication even after cell entry (Paul, 2003).
Unfortunately, while the cellular response to HIV can slow its progression, the virus has adapted methods to avoid total defeat. While the CTL response is high, nef's downregulation of MHC-I molecules in infected cells helps virally-infected cells from being spotted by cytotoxic CD8 cells (Rubbert et al, 2006). In order to mount an effective cytotoxic response, the CD8+ cells require interaction with virus-specific CD4+ T cells. It is thought that the HIV virus preferentially kills HIV-specific CD4+ cells early on in the course of the infection to minimize the immune response (Paul, 2003).
Paul, William ed. Fundamental Immunology. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2003.
Rubbert, A., et al . 2006. Pathogenesis of HIV-1 Infection. In: Hoffmann, C., Rockstroh, J., Kamps, B., editors. HIV Medicine 2006. Flying Publisher. <http://www.hivmedicine.com/index.htm>. (5 May 2007).