Multicolor Flow Cytometric Analyses of CD4+ T Cell Responses to Mycobacterium tuberculosis-Related Latent Antigens
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概要
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Although IFN-γ release assays (IGRAs) provide increased specificity over tuberculin skin tests, the early and sensitive detection of reactivation of latently infected Mycobacterium tuberculosis is required to control tuberculosis (TB). Recently, a multicolor flow cytometry has been developed to study CD4+ T cell cytokine responses (IFN-γ/IL-2/TNF-α) to purified protein derivatives (PPD) and M. tuberculosis-specific antigens (ESAT-6/CFP-10) and provided useful information regarding anti-TB immunity. However, the diagnostic relevancy remains uncertain. Here, we analyzed three additional CD4+ T cell cytokine responses (IL-10/IL-13/IL-17) to latent mycobacterial antigens (α-crystallin, methylated heparin-binding hemagglutinin [HBHA], and mycobacterial DNA-binding protein 1 [MDP-1]) as well as PPD and ESAT-6/CFP-10 in 12 IGRA+ TB cases and 8 healthy controls. No significant difference in IFN-γ response was observed between TB cases and controls, which was likely due to the high variation among the individuals. However, we found a significant increase over healthy controls in (i) the IL-2 response to HBHA in recovery stage TB cases, (ii) the number of M. tuberculosis-specific polyfunctional CD4+ T cells in on-treatment and recovery stage cases, and (iii) the IL-17 response to HBHA and MDP-1 in on-treatment and recovery stage cases. These results suggest that a combination of these T cell cytokine parameters could aid in accurate diagnosis of latent TB infection.
著者
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Ariyoshi Koya
Department Of Clinical Medicine Institute Of Tropical Medicine Nagasaki University
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TSUNETSUGU-YOKOTA Yasuko
Department of Immunology, National Institute of Infectious Diseases
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Hoshino Yoshihiko
Department Of Infectious Diseases Institute Of Medical Science University Of Tokyo
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星野 芳彦
Division Of Pulmonary & Critical Care Medicine New York University Medical Center
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Yamashita Yoshiro
Department Of Biology Faculty Of Science Kumamoto University
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MATSUMOTO Sokichi
Department of Oral Microbiology, School of Dentistry, Nagasaki University
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Makino Masahiko
Department Of Microbiology Leprosy Research Center National Institute Of Infectious Disease
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Nagai Hideaki
Center for Respiratory Medicine, National Hospital Organization Tokyo National Hospital
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Oka Mayuko
Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University
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Ariga Haruyuki
Center for Respiratory Medicine, National Hospital Organization Tokyo National Hospital
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Makino Masahiko
Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases
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Hoshino Yoshihiko
Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases
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Ariyoshi Koya
Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University
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Yamashita Yoshiro
Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University
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Matsumoto Sokichi
Department of Bacteriology, Osaka City University Graduate School of Medicine
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