Target epitopes of HTLV-1 recognized by class I MHC-restricted cytotoxic T lymphocytes in patients with myelopathy and spastic paraparesis and infected patients with autoimmune disorders.
Human T-cell lymphotropic virus type I (HTLV-1) causes adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The different patterns of clinical diseases are thought to be linked to immunogenetic host factors. A variety of autoimmune diseases, such as Sjögren's syndrome, have been reported in persons infected with HTLV-1, although the precise relationship between these disorders and HTLV-1 infection remains unknown. There is no report on the repertoire of HTLV-1-specific CD8+ T-cells in HAM/TSP patients or carriers with autoimmune diseases, both characterized by an abnormal immune state. In this study, to characterize HTLV-1-specific CD8+ T-cells in asymptomatic HTLV-1 carriers, HAM/TSP patients and carriers with autoimmune diseases, we examined the frequency and diversity of HTLV-1-specific CD8+ T-cells using HTLV-1 tetramers. HTLV-1 Env-specific CD8+ T-cells were significantly more frequent in HAM/TSP and carriers with autoimmune diseases compared with asymptomatic HTLV-1 carriers, while the frequency of HTLV-1 Tax-specific CD8+ T-cells was not significantly different among them. CD8+ cells binding to HTLV-1 Tax tetramers in carriers with autoimmune diseases were significantly reduced compared with HAM/TSP patients. This study demonstrates the importance of CD8+ T-cells recognizing HTLV-1 Env-tetramers in HAM/TSP patients and carriers with autoimmune diseases, thereby suggesting that the diversity, frequency and repertoire of HTLV-1 Env-specific CD8+ T-cell clones may be related to the hyperimmune response in HAM/TSP and carriers with autoimmune diseases, although different immunological mechanisms may mediate the hyperimmunity in these conditions.
Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Tomohiro
T
Kozako
Masaki
M
Akimoto
Shingo
S
Toji
Yohann
Y
White
Susumu
S
Suzuki
Takehiro
T
Arima
Yukio
Y
Suruga
Kakushi
K
Matsushita
Hiroshi
H
Shimeno
Shinji
S
Soeda
Ryuji
R
Kubota
Shuji
S
Izumo
Kimiharu
K
Uozumi
Naomichi
N
Arima
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000276:immunology*; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D016356:Gene Products, tax / Q000276:immunology / Q000378:metabolism; D014644:Genetic Variation; D015234:HLA-A Antigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006650:Histocompatibility Testing; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D000939:Epitopes; D016356:Gene Products, tax; D015234:HLA-A Antigens; D014759:Viral Envelope Proteins; C514970:tax protein, Human T-lymphotrophic virus 1