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

• Published in: Journal of general virology Vol. 86; no. 5; pp. 1515 - 1523
• Main Authors: Asquith, Becca, Mosley, Angelina J, Barfield, Anna, Marshall, Sara E. F, Heaps, Adrian, Goon, Peter, Hanon, Emmanuel, Tanaka, Yuetsu, Taylor, Graham P, Bangham, Charles R. M
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.05.2005; Society for General Microbiology
• Subjects: Adult; Aged; Biological and medical sciences; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - immunology; DNA, Viral - analysis; Female; Fundamental and applied biological sciences. Psychology; Human T-lymphotropic virus 1 - immunology; Human T-lymphotropic virus 1 - physiology; Humans; Male; Microbiology; Middle Aged; Miscellaneous; Proviruses - isolation & purification; Viral Load; Virology; Virus; Deltaretrovirus; Microbiology; Efficiency; Retroviridae; Antiviral; HTLV-I virus; Provirus; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.80766-0

1 Department of Immunology, Imperial College, London, UK 2 Department of Genito-Urinary Medicine and Communicable Diseases, Imperial College, London, UK 3 GlaxoSmithKline Biologicals, Belgium 4 Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Japan Correspondence Becca Asquith b.asquith{at}imperial.ac.uk 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 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. Supplementary material is available in JGV Online. These authors contributed equally to this work.