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The Avidity and Lytic Efficiency of the CTL Response to HTLV-1¹

Tarek Kattan^2,*, Aidan MacNamara^2,*, Aileen G. Rowan^2,*, Hirohisa Nose^*, Angelina J. Mosley, Yuetsu Tanaka, Graham P. Taylor, Becca Asquith^* and Charles R. M. Bangham^3,*

^* Department of Immunology, Wright-Fleming Institute, Imperial College London, United Kingdom; Department of Neuroinflammation, University College London Institute of Neurology, London, United Kingdom; Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Japan; and Department of Genito-Urinary Medicine and Communicable Diseases, Imperial College London, United Kingdom

In human T-lymphotropic virus type 1 (HTLV-1) infection, a high frequency of HTLV-1-specific CTLs can co-exist stably with a high proviral load and the proviral load is strongly correlated with the risk of HTLV-1-associated inflammatory diseases. These observations led to the hypothesis that HTLV-1 specific CTLs are ineffective in controlling HTLV-1 replication but contribute to the pathogenesis of the inflammatory diseases. But evidence from host and viral immunogenetics and gene expression microarrays suggests that a strong CTL response is associated with a low proviral load and a low risk of HAM/TSP. Here, we quantified the frequency, lytic activity and functional avidity of HTLV-1-specific CD8⁺ cells in fresh, unstimulated PBMCs from individuals with natural HTLV-1 infection. The lytic efficiency of the CD8⁺ T cell response—the fraction of autologous HTLV-1-expressing cells eliminated per CD8⁺ cell per day—was inversely correlated with both the proviral load and the rate of spontaneous proviral expression. The functional avidity of HTLV-1-specific CD8⁺ cells was strongly correlated with their lytic efficiency. We conclude that efficient control of HTLV-1 in vivo depends on the CTL lytic efficiency, which depends in turn on CTL avidity of Ag recognition. CTL quality determines the position of virus-host equilibrium in persistent HTLV-1 infection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Wellcome Trust (UK) and the National Institute of Health Research Biomedical Research Centre funding scheme.

² These authors contributed equally: order is alphabetical.

³ Address correspondence and reprint requests to Dr. Charles Bangham, Department of Immunology, Wright-Fleming Institute, Imperial College London, Norfolk Place, London, W2 1PG. E-mail address: c.bangham{at}imperial.ac.uk.

⁴ Abbreviations used in this paper used in this paper: HTLV-1, human T cell lymphotropic virus; ATLL, adult T-cell leukaemia/lymphoma; HAM/TSP, HTLV-1-associated myelopathy/tropical spastic paraparesis; AC, asymptomatic carrier; SFC, spot forming cells.