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.
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.
Asquith
Becca
B
Department of Immunology, Imperial College, London, UK.
Mosley
Angelina J
AJ
Department of Immunology, Imperial College, London, UK.
Barfield
Anna
A
Department of Genito-Urinary Medicine and Communicable Diseases, Imperial College, London, UK.
Marshall
Sara E F
SEF
Department of Immunology, Imperial College, London, UK.
Heaps
Adrian
A
Department of Immunology, Imperial College, London, UK.
Goon
Peter
P
Department of Immunology, Imperial College, London, UK.
Hanon
Emmanuel
E
GlaxoSmithKline Biologicals, Belgium.
Tanaka
Yuetsu
Y
Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Japan.
Taylor
Graham P
GP
Department of Genito-Urinary Medicine and Communicable Diseases, Imperial College, London, UK.
Bangham
Charles R M
CRM
Department of Immunology, Imperial College, London, UK.
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000302:isolation & purification; D019562:Viral Load
D004279:DNA, Viral