Suppressed induction of mycobacterial antigenspecific Th1-type CD4+ T cells in the lung after pulmonary mycobacterial infection

Ayano Yahagi, Masayuki Umemura, Toshiki Tamura, Ai Kariyone, M. Dilara Begum, Kazuyoshi Kawakami, Yuko Okamoto, Satoru Hamada, Kiyotetsu Oshiro, Hideyasu Kohama, Takeshi Arakawa, Naoya Ohara, Kiyoshi Takatsu, Goro Matsuzaki

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11 Citations (Scopus)

Abstract

Although the importance of Th1-type immune response in protection against mycobacterial infection is well recognized, its regulatory mechanism in the Mycobacterium tuberculosis (Mtb)-infected lung is not well characterized. To address this issue, we analyzed kinetics of induction of mycobacterial antigen-specific CD41 Th1 T cells after mycobacterial infection in P25 TCR-transgenic (Tg) mice which express TCR α and b chains from a mycobacterial Ag85B-specific MHC class II Ab-restricted CD4+ T-cell clone. To supply normal regulatory T-cell repertoire, we transferred normal spleen T cells into the P25 TCR-Tg mice before infection. High dose subcutaneous infection with Mtb or Mycobacterium bovis bacillus Calmette-Guérin (BCG) induced P25 TCR-Tg CD4+ Th1 cells within a week. In contrast, high-dose Mtb or BCG infection into the lung failed to induce P25 TCR-Tg CD4+ Th1 cells at the early stage of the infection. Furthermore, low-dose Mtb infection into the lung induced P25 TCR-Tg CD4+ Th1 cells on day 21 in the mediastinal lymph node but not in the lung. IL-10 was partially involved in the suppression of Th1 induction in the lung because pretreatment of mice with anti-IL-10 antibody resulted in increase of P25 TCR-Tg CD4+ Th1 cells in the Mtb-infected lung on day 21 of the infection, whereas neutralization of transforming growth factor-b, another important suppressive cytokine in the lung, showed no effects on the Th1 induction. Our data suggest that induction of anti-mycobacterial CD4+ Th1 cells is suppressed in the mycobacteria-infected lung partially by IL-10.

Original languageEnglish
Pages (from-to)307-318
Number of pages12
JournalInternational immunology
Volume22
Issue number4
DOIs
Publication statusPublished - 2010 Feb 18

Keywords

  • Infection
  • Lung
  • Mycobacterium
  • T1
  • TCR transgenic mouse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Yahagi, A., Umemura, M., Tamura, T., Kariyone, A., Begum, M. D., Kawakami, K., Okamoto, Y., Hamada, S., Oshiro, K., Kohama, H., Arakawa, T., Ohara, N., Takatsu, K., & Matsuzaki, G. (2010). Suppressed induction of mycobacterial antigenspecific Th1-type CD4+ T cells in the lung after pulmonary mycobacterial infection. International immunology, 22(4), 307-318. https://doi.org/10.1093/intimm/dxq010