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Prepublished online as a Blood First Edition Paper on January 30, 2003; DOI 10.1182/blood-2002-09-2855.
Submitted September 25, 2002
Accepted January 23, 2003
Low frequency of CD94/NKG2A-positive T lymphocytes in HTLV-1 associated myelopathy/tropical spastic paraparesis patients 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*
Department of Immunology, Imperial College London, London, United Kingdom
Institut de Pharmacologie Moleculaire et Cellulaire, CNRS UMR 6097, Sophia Antipolis University, Valbonne, France
Genito-Urinary Medicine and Communicable diseases, Imperial College London, London, United Kingdom
Third Department of Internal Medicine, Kagoshima University, Kagoshima, Japan
Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science, Nishihara, Okinawa, Japan
Department of Medical Informatics, Kagoshima University, Kagoshima, Kyushu, Japan
* Corresponding author; email: c.bangham{at}imperial.ac.uk.
Human NK cell receptors are expressed by natural killer cells and some T cells, primarily TCR+CD8+ cytotoxic T lymphocytes (CTL). Inhibitory NK cell receptors (iNKR) 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 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients but not in asymptomatic HTLV-1 carriers. These cells were either   or   T cells. T-cell receptor (TCR) V-specific RT-PCR and spectratyping analysis revealed that the TCR repertoire in directly isolated HLA-E-tetramer+ cells from PBMC was skewed in both HTLV-1 infected and normal individuals. However, oligoclonally or monoclonally expanded TCR Vs were more frequently detected within HTLV-1 infected individuals than normal controls. Importantly, HLA-E-tetramer+ or NKG2A+ T cells from HTLV-1 patients do not express Tax and display different TCR usage than 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 anti-viral 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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