Suppressed induction of mycobacterial antigenspecific T_h1-type CD4⁺ T cells in the lung after pulmonary mycobacterial infection

Although the importance of T_h1-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 T_h1 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 A^b-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⁺ T_h1 cells within a week. In contrast, high-dose Mtb or BCG infection into the lung failed to induce P25 TCR-Tg CD4⁺ T_h1 cells at the early stage of the infection. Furthermore, low-dose Mtb infection into the lung induced P25 TCR-Tg CD4⁺ T_h1 cells on day 21 in the mediastinal lymph node but not in the lung. IL-10 was partially involved in the suppression of T_h1 induction in the lung because pretreatment of mice with anti-IL-10 antibody resulted in increase of P25 TCR-Tg CD4⁺ T_h1 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 T_h1 induction. Our data suggest that induction of anti-mycobacterial CD4⁺ T_h1 cells is suppressed in the mycobacteria-infected lung partially by IL-10.