期刊
INTERNATIONAL IMMUNOLOGY
卷 22, 期 12, 页码 915-925出版社
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxq446
关键词
Mycobacterium; PD-1; persistent infection; T(h)1 immunity
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Japan Society for the Promotion of Science
- Ministry of Health, Labour and Welfare, Japan
- Waksman Foundation of Japan
- Grants-in-Aid for Scientific Research [22390082, 21590479] Funding Source: KAKEN
A major concern still prevails as to the reason why various mycobacteria are able to persist within infected host in which protective immunity is generated. To address this question, we monitored the generation of protective T cells during infection with Mycobacterium bovis bacillus Calmette-Guerin (BCG). CD4(+) T cells obtained 3 weeks after infection conferred protection against Mycobacterium tuberculosis challenge and produced IFN-gamma and tumor necrosis factor (TNF)-alpha upon antigen stimulation. However, these abilities were decreased after 6 weeks of infection even though BCG was not thoroughly eliminated from the host. We analyzed the expression of ligands for the CD28/CTLA-4 family receptors on antigen-presenting cells and found that the expression of PD-L1, a ligand for programmed cell death-1 (PD-1), was up-regulated later than 3 weeks of infection. We also found that bacterial numbers in the spleen of PD-1-deficient mice were significantly reduced compared with wild-type mice at 6 and 12 weeks after BCG infection. Furthermore, CD4(+) T cells of PD-1-deficient mice showed a higher ability to confer protection and produce IFN-gamma and TNF-alpha even at 12 weeks after infection. These results indicate that the PD-1-PD-L1 pathway impairs T(h)1 immunity in the late stage of BCG infection, thereby facilitating the bacterial persistence in the host.
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