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Human T Cell Lymphotropic Virus Type I (HTLV-I)-Specific CD4⁺ T Cells: Immunodominance Hierarchy and Preferential Infection with HTLV-I¹

Peter K. C. Goon^*, Tadahiko Igakura^*, Emmanuel Hanon^*, Angelina J. Mosley^*, Anna Barfield^*, Amanda L. Barnard^*, Lambrini Kaftantzi^*, Yuetsu Tanaka, Graham P. Taylor, Jonathan N. Weber and Charles R. M. Bangham^2,*

^* Department of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College London, London, United Kingdom; and Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science, Faculty of Medicine, University of The Ryukus, Okinawa, Japan

CD4⁺ T cells predominate in early lesions in the CNS in the inflammatory disease human lymphotropic T cell virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but the pathogenesis of the disease remains unclear and the HTLV-I-specific CD4⁺ T cell response has been little studied. We quantified the IFN--producing HTLV-I-specific CD4⁺ T cells, in patients with HAM/TSP and in asymptomatic carriers with high proviral load, to test two hypotheses: that HAM/TSP patients and asymptomatic HTLV-I carriers with a similar proviral load differ in the immunodominance hierarchy or the total frequency of specific CD4⁺ T cells, and that HTLV-I-specific CD4⁺ T cells are preferentially infected with HTLV-I. The strongest CD4⁺ T cell response in both HAM/TSP patients and asymptomatic carriers was specific to Env. This contrasts with the immunodominance of Tax in the HTLV-I-specific CD8⁺ T cell response. The median frequency of HTLV-I-specific IFN-⁺ CD4⁺ T cells was 25-fold greater in patients with HAM/TSP (p = 0.0023, Mann-Whitney) than in asymptomatic HTLV-I carriers with a similar proviral load. Furthermore, the frequency of CD4⁺ T cells infected with HTLV-I (expressing Tax protein) was significantly greater (p = 0.0152, Mann-Whitney) among HTLV-I-specific cells than CMV-specific cells. These data were confirmed by quantitative PCR for HTLV-I DNA. We conclude that the high frequency of specific CD4⁺ T cells was associated with the disease HAM/TSP, and did not simply reflect the higher proviral load that is usually found in HAM/TSP patients. Finally, we conclude that HTLV-I-specific CD4⁺ T cells are preferentially infected with HTLV-I.

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