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 a or ?d T cells. T-cell receptor (TCR) V-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 Vwere 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.
Saito, M.; Braud, V.M.; Goon, P.; Hanon, E.; Taylor, G.P.; Saito, A.; Eiraku, N.; Tanaka, Y.; Usuku, K.; Weber, J.N.; Osame, M.; Bangham, C.R.M. Low frequency of CD94/NKG2A+ T lymphocytes in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis, but not in asymptomatic carriers. Blood (2003) 102 (2) 577-584. [DOI: 10.1182/blood-2002-09-2855]