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 language | English |
|---|---|
| Pages (from-to) | 307-318 |
| Number of pages | 12 |
| Journal | International Immunology |
| Volume | 22 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Feb 18 2010 |
| Externally published | Yes |
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Keywords
- Infection
- Lung
- Mycobacterium
- T1
- TCR transgenic mouse
ASJC Scopus subject areas
- Immunology
Cite this
Suppressed induction of mycobacterial antigenspecific Th1-type CD4+ T cells in the lung after pulmonary mycobacterial infection. / Yahagi, Ayano; Umemura, Masayuki; Tamura, Toshiki; Kariyone, Ai; Begum, M. Dilara; Kawakami, Kazuyoshi; Okamoto, Yuko; Hamada, Satoru; Oshiro, Kiyotetsu; Kohama, Hideyasu; Arakawa, Takeshi; Oohara, Naoya; Takatsu, Kiyoshi; Matsuzaki, Goro.
In: International Immunology, Vol. 22, No. 4, 18.02.2010, p. 307-318.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Suppressed induction of mycobacterial antigenspecific Th1-type CD4+ T cells in the lung after pulmonary mycobacterial infection
AU - Yahagi, Ayano
AU - Umemura, Masayuki
AU - Tamura, Toshiki
AU - Kariyone, Ai
AU - Begum, M. Dilara
AU - Kawakami, Kazuyoshi
AU - Okamoto, Yuko
AU - Hamada, Satoru
AU - Oshiro, Kiyotetsu
AU - Kohama, Hideyasu
AU - Arakawa, Takeshi
AU - Oohara, Naoya
AU - Takatsu, Kiyoshi
AU - Matsuzaki, Goro
PY - 2010/2/18
Y1 - 2010/2/18
N2 - 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.
AB - 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.
KW - Infection
KW - Lung
KW - Mycobacterium
KW - T1
KW - TCR transgenic mouse
UR - http://www.scopus.com/inward/record.url?scp=77954072723&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954072723&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxq010
DO - 10.1093/intimm/dxq010
M3 - Article
C2 - 20167585
AN - SCOPUS:77954072723
VL - 22
SP - 307
EP - 318
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 4
ER -