Multicolor Flow Cytometric Analyses of CD4+ T Cell Responses to Mycobacterium tuberculosis-Related Latent Antigens

Japanese Journal of Infectious Diseases

Masahiko Makino²  Yoshihiko Hoshino²  Yasuko Tsunetsugu-Yokota⁶  Sokichi Matsumoto⁴  Mayuko Oka³  Yoshiro Yamashita⁵  Koya Ariyoshi⁵  Haruyuki Ariga¹  Hideaki Nagai¹ 

[1] Center for Respiratory Medicine, National Hospital Organization Tokyo National Hospital;Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases;Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University;Department of Bacteriology, Osaka City University Graduate School of Medicine;Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University;Department of Immunology, National Institute of Infectious Diseases

关键词: tuberculosis;    T cell cytokine response;    latent infection;   

DOI  :  10.7883/yoken.66.207

学科分类：传染病学

来源: National Institute of Infectious Diseases

【 摘 要 】

References(39)Cited-By(6)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.

【 授权许可】

Unknown