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Prepublished online as a Blood First Edition Paper on January 30, 2003; DOI 10.1182/blood-2002-09-2855.

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2002-09-2855v1
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Blood, 15 July 2003, Vol. 102, No. 2, pp. 577-584

IMMUNOBIOLOGY

Low frequency of CD94/NKG2A+ T lymphocytes in patients with HTLV-1–associated myelopathy/tropical spastic paraparesis, but not in asymptomatic carriers

Mineki Saito, Veronique M. Braud, Peter Goon, Emmanuel Hanon, Graham P. Taylor, Akiko Saito, Nobutaka Eiraku, Yuetsu Tanaka, Koichiro Usuku, Jonathan N. Weber, Mitsuhiro Osame, and Charles R. M. Bangham

From the Department of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College London, St Mary's Campus, London, United Kingdom; Institut de Pharmacologie Moleculaire et Cellulaire, CNRS UMR 6097, Sophia Antipolis, Valbonne, France; Third Department of Internal Medicine and Department of Medical Informatics, Faculty of Medicine, Kagoshima University, Kagoshima, Japan; and Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan

Human natural killer (NK)–cell receptors are expressed by NK cells and some T cells, primarily TCR+CD8+ cytotoxic T lymphocytes (CTLs). Inhibitory NK cell receptors (iNKRs) can down-regulate antigen-mediated T-cell effector functions, including cytotoxic activity and cytokine release. In the present study we demonstrate that CD3+ T cells that bind tetramers of HLA-E and express its ligand, the NK-cell inhibitory receptor CD94/NKG2A, were significantly decreased in frequency in patients with human T-cell lymphotropic virus 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) but not in asymptomatic HTLV-1 carriers. These cells were either {alpha}{beta} or {gamma}{delta} T cells. T-cell receptor (TCR) V{beta}-specific reverse transcription–polymerase chain reaction and spectratyping analysis revealed that the TCR repertoire in directly isolated HLA-E tetramer–positive cells from peripheral blood mononuclear cells was skewed in both HTLV-1–infected and healthy individuals. However, oligoclonally or monoclonally expanded levels of TCR V{beta}were more frequently detected within HTLV-1–infected individuals than healthy controls. Importantly, HLA-E tetramer–positive or NKG2A+ T cells from HTLV-1 patients do not express Tax and display different TCR usage from the immunodominant Tax11-19–specific CD8+ T cells, suggesting that they do not encounter HTLV-1–infected cells. The expression of NK cell–associated receptors by clonally expanded CD8+ T cells during chronic viral infection suggests that these receptors play a role in regulating CD8+ T cell–mediated antiviral immune responses and that a decrease of this cell subset results in an increased risk of inflammatory diseases such as HAM/TSP.


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