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* Division of Host Response, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University;
International Island and Community Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University;
Department of Hematology and Immunology, Kagoshima University Hospital, and
Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; and
¶ Medical and Biological Laboratories, Co., Ltd, Nagoya, Japan
Human T cell lymphotropic virus type 1 (HTLV-1)-specific CTL are thought to be immune effectors that reduce the risk of adult T cell leukemia (ATL). However, in vivo conditions of anti-HTLV-1 CTL before and after ATL development have yet to be determined. To characterize anti-HTLV-1 CTL in asymptomatic HTLV-1 carriers (AC) and ATL patients, we analyzed the frequency and diversity of HTLV-1-specific CD8+ T cells in PBMC of 35 AC and 32 ATL patients using 16 distinct epitopes of HTLV-1 Tax or Env/HLA tetramers along with intracellular cytolytic effector molecules (IFN-
, perforin, and granzyme B). Overall frequency of subjects possessing Tax-specific CD8+ T cells was significantly lower in ATL than AC (53 vs 90%; p = 0.001), whereas the difference in Env-specific CD8+ T cells was not statistically significant. AC possessed Tax11–19/HLA-A*0201-specific tetramer+ cells by 90% and Tax301–309/HLA-A*2402-specific tetramer+ cells by 92%. Some AC recognized more than one epitope. In contrast, ATL recognized only Tax11–19 with HLA-A*0201 and Tax301–309 with HLA-A*2402 at frequencies of 30 and 55%. There were also significant differences in percentage of cells binding Tax11–19/HLA-A*0201 and Tax301–309/HLA-A*2402 tetramers between AC and ATL. Anti-HTLV-1 Tax CD8+ T cells in AC and ATL produced IFN- in response to Tax. In contrast, perforin and granzyme B expression in anti-HTLV-1 CD8+ T cells of ATL was significant lower than that of AC. Frequency of Tax-specific CD8+ T cells in AC was related to proviral load in HLA-A*0201. These results suggest that decreased frequency, diversity, and function of anti-HTLV-1 Tax CD8+ T cell clones may be one of the risks of ATL development.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported in part by Grants-in-Aid for Scientific Research on Priority Area for Cancer Research (122198232 and 12218104) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
2 Address correspondence and reprint requests to Dr. Naomichi Arima, Division of Host Response, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. E-mail address: nao{at}m2.kufm.kagoshima-u.ac.jp
3 Abbreviations used in this paper: ATL, adult T cell leukemia; HTLV-1, human T cell lymphotropic virus type 1; AC, asymptomatic HTLV-1 carrier; 7-AAD, 7-amino-actinomycin D.
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  Y. Enose-Akahata, U. Oh, C. Grant, and S. Jacobson Retrovirally induced CTL degranulation mediated by IL-15 expression and infection of mononuclear phagocytes in patients with HTLV-I-associated neurologic disease Blood, September 15, 2008; 112(6): 2400 - 2410. [Abstract] [Full Text] [PDF]
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