Functional impairment of Tax-specific but not cytomegalovirus-specific CD8+ T lymphocytes in a minor population of asymptomatic human T-cell leukemia virus type 1-carriers

• Published in: Retrovirology Vol. 8; no. 1; p. 100
• Main Authors: Takamori, Ayako, Hasegawa, Atsuhiko, Utsunomiya, Atae, Maeda, Yasuhiro, Yamano, Yoshihisa, Masuda, Masato, Shimizu, Yukiko, Tamai, Yotaro, Sasada, Amane, Zeng, Na, Choi, Ilseung, Uike, Naokuni, Okamura, Jun, Watanabe, Toshiki, Masuda, Takao, Kannagi, Mari
• Format: Journal Article
• Language: English
• Published: England BioMed Central 07.12.2011; BioMed Central Ltd; BMC
• Subjects: Antigens, CD - metabolism; Antigens, Differentiation, T-Lymphocyte - metabolism; Asymptomatic Infections; Cancer; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cell Proliferation; Cells, Cultured; Colleges & universities; Cytomegalovirus - immunology; Cytotoxicity; Gene Products, tax - immunology; HIV; Hospitals; HTLV-I Infections - immunology; Human immunodeficiency virus; Human T-lymphotropic virus 1 - immunology; Humans; Interferon-gamma - metabolism; Lectins, C-Type - metabolism; Leukemia; Leukemia-Lymphoma, Adult T-Cell - immunology; Load; Lymphocyte Activation; Lysosomal-Associated Membrane Protein 1 - metabolism; Paraparesis, Tropical Spastic - immunology; Paraparesis, Tropical Spastic - virology; Phosphoproteins - immunology; Science; T-Lymphocytes, Cytotoxic - immunology; Viral infections; Viral Matrix Proteins - immunology
• ISSN: 1742-4690; 1742-4690
• DOI: 10.1186/1742-4690-8-100

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a small percentage of infected individuals. ATL is often associated with general immune suppression and an impaired HTLV-1-specific T-cell response, an important host defense system. We previously found that a small fraction of asymptomatic HTLV-1-carriers (AC) already showed impaired T-cell responses against the major target antigen, Tax. However, it is unclear whether the impaired HTLV-1 Tax-specific T-cell response in these individuals is an HTLV-1-specific phenomenon, or merely reflects general immune suppression. In this study, in order to characterize the impaired HTLV-1-specific T-cell response, we investigated the function of Tax-specific CD8+ T-cells in various clinical status of HTLV-1 infection. By using tetramers consisting of HLA-A*0201, -A*2402, or -A*1101, and corresponding Tax epitope peptides, we detected Tax-specific CD8+ T-cells in the peripheral blood from 87.0% of ACs (n = 20/23) and 100% of HAM/TSP patients (n = 18/18) tested. We also detected Tax-specific CD8+ T-cells in 38.1% of chronic type ATL (cATL) patients (n = 8/21), although its frequencies in peripheral blood CD8+ T cells were significantly lower than those of ACs or HAM/TSP patients. Tax-specific CD8+ T-cells detected in HAM/TSP patients proliferated well in culture and produced IFN-γ when stimulated with Tax peptides. However, such functions were severely impaired in the Tax-specific CD8+ T-cells detected in cATL patients. In ACs, the responses of Tax-specific CD8+ T-cells were retained in most cases. However, we found one AC sample whose Tax-specific CD8+ T-cells hardly produced IFN-γ, and failed to proliferate and express activation (CD69) and degranulation (CD107a) markers in response to Tax peptide. Importantly, the same AC sample contained cytomegalovirus (CMV) pp65-specific CD8+ T-cells that possessed functions upon CMV pp65 peptide stimulation. We further examined additional samples of two smoldering type ATL patients and found that they also showed dysfunctions of Tax-specific but not CMV-specific CD8+ T-cells. These findings indicated that Tax-specific CD8+ T-cells were scarce and dysfunctional not only in ATL patients but also in a limited AC population, and that the dysfunction was selective for HTLV-1-specifc CD8+ T-cells in early stages.