A functional CD8 + cell assay reveals individual variation in CD8 + cell antiviral efficacy and explains differences in human T-lymphotropic virus type 1 proviral load
2005
The
CD8+ lymphocyte response is a main component of host immunity, yet it is difficult to quantify its contribution to the control of persistent viruses. Consequently, it remains controversial as to whether
CD8+ cells have a biologically significant impact on viral burden and disease progression in infections such as
human immunodeficiency virus-1and
human T-lymphotropic virustype I (HTLV-I). Experiments to ascertain the impact of
CD8+ cells on viral burden based on
CD8+ cell frequency or specificity alone give inconsistent results. Here, an alternative approach was developed that directly quantifies the impact of
CD8+ lymphocytes on HTLV-I proviral burden by measuring the rate at which HTLV-I-infected CD4+ cells were cleared by autologous
CD8+ cells ex vivo. It was demonstrated that
CD8+ cells reduced the lifespan of infected CD4+ cells to 1 day, considerably shorter than the 30 day lifespan of uninfected cells in vivo. Furthermore, it was shown that HTLV-I-infected individuals vary considerably in the rate at which their
CD8+ cells clear infected cells, and that this was a significant predictor of their HTLV-I proviral load. Forty to 50 % of between-individual variation in HTLV-I proviral load was explained by variation in the rate at which
CD8+ cells cleared infected cells. This novel approach demonstrates that
CD8+ cells are a major determinant of HTLV-I proviral load. This assay is applicable to quantifying the
CD8+ cell response to other viruses and malignancies and may be of particular importance in assessing vaccines.
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