1887

Abstract

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-1 and human T-lymphotropic virus type 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 . 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 . 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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2005-05-01
2019-08-26
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vol. , part 5, pp. 1515 - 1523

Table showing the rate of clearance of autologous and allogenic target cells and the estimation of the number of infected cells cleared per HTLV-I-specific CD8 cell per day [PDF](159 KB)



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