Cytolytic CD4 T cells - Defining potential strategies for therapeutic HIV vaccines
Immunology
Final Report Abstract
The development of antiretroviral therapies (ART) has significantly improved the lives of people infected with HIV. The life expectancy of people on ART is no different from that of uninfected people. Nevertheless, it is still not possible to eliminate the virus in the body of infected persons even with ART. In the presented project, a subpopulation of CD4 T cells is identified which is able to recognize and eliminate cells infected with the virus in the lymphatic B cell follicle. The cytolytic activity could be demonstrated by the expression of granzyme B, perforin and interferon gamma. In an in vitro experiment, the CD4 T cell subpopulation showed a higher cytolytic activity than CD8 T cells, which normally regulate the elimination of infected cells. This led to the question of whether the activity of CD8 cells is influenced by ARTs. It could be shown that the form of ART used has an influence on the expression of cytokines. When integrase inhibitors are used, the expression of the four cytokines tested was detected in significantly fewer CD8 T cells compared to treatments with protease inhibitors and nonnucleoside retrotranscriptase inhibitors. The results obtained in this project provide a basis for using a combination of therapeutic options to achieve elimination of HIV after infection. In addition, targeted control of the CD4 T cell subpopulation in the lymphoid B cell follicle can be used as a potential vaccine strategy.
Publications
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Reduction of CD8 T Cell Functionality but Not Inhibitory Capacity by Integrase Inhibitors. Journal of Virology, 96(5).
Richter, Enrico; Bornemann, Lea; Korencak, Marek; Alter, Galit; Schuster, Marc; Esser, Stefan; Boesecke, Christoph; Rockstroh, Juergen; Gunzer, Matthias & Streeck, Hendrik
