Journal
BLOOD
Volume 114, Issue 15, Pages 3208-3215Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-02-203042
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Funding
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology, Japanese Ministry of Health, Labour, and Welfare [H21-NANCHIIPPAN-008]
- National Institute of Biomedical Innovation
- Uehara Memorial Foundation
- Nagao Takeshi Nanbyo Foundation
- Kanagawa Nanbyo Foundation
- Mishima Kaiun Memorial Foundation
- Takeda Science Foundation
- ITSUU Laboratory Research Foundation
- Kanae Foundation for Life and Socio-Medical Science
- Japan Research Foundation for Clinical Pharmacology
- Kanagawa Academy of Science and Technology
- Japan College of Rheumatology
- Nakajima Foundation
- Osaka Foundation for Cancer Research
- New Energy and Industrial Technology Development Organization
- Mochida Pharmaceutical Company Ltd
- Kanagawa High-Technology Foundation
- Kanto Bureau of Economy, Trade and Industry
- Mitsui Life Insurance Company Ltd
- Heiwa Nakajima Foundation
- Sagawa Foundation for Promotion of Cancer Research
- Tokyo Biochemical Research Foundation
- Grants-in-Aid for Scientific Research [20249052] Funding Source: KAKEN
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Invariant natural killer T (iNKT) cells are unique T cells that regulate the immune response to microbes, cancers, and autoimmunity. We assessed the characteristics of iNKT cells from persons infected with human T-lymphotropic virus type 1 (HTLV-1). Whereas most infected persons remain asymptomatic carriers (ACs) throughout their lives, a small proportion, usually with high equilibrium proviral loads, develop 2 diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia (ATL). We demonstrated that the frequency of iNKT, NK, and dendritic cells in the peripheral blood of HAM/TSP and ATL patients is decreased. We also observed an inverse correlation between the iNKT cell frequency and the HTLV-1 proviral load in the peripheral blood of infected persons. Notably, in vitro stimulation of peripheral blood cells with alpha-galactosylceramide led to an increase in the iNKT cell number and a subsequent decrease in the HTLV-1-infected T-cell number in samples from ACs but not HAM/TSP or ATL patients. Our results suggest that iNKT cells contribute to the immune defense against HTLV-1, and iNKT-cell depletion plays an important role in the pathogenesis of HAM/TSP and ATL. Therefore, iNKT cell-based immunotherapy may be an effective strategy for preventing these HTLV-1-associated disorders. (Blood. 2009; 114: 3208-3215)
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