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

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. © The Japanese Society for Immunology. 2010. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.