title: Suppressed induction of mycobacterial antigen-specific Th1-type CD4+ T cells in the lung after pulmonary mycobacterial infection.
abstract: Although the importance of T(h)1-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 CD4(+) T(h)1 T cells after mycobacterial infection in P25 TCR-transgenic (Tg) mice which express TCR alpha and beta 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(h)1 cells within a week. In contrast, high-dose Mtb or BCG infection into the lung failed to induce P25 TCR-Tg CD4(+) T(h)1 cells at the early stage of the infection. Furthermore, low-dose Mtb infection into the lung induced P25 TCR-Tg CD4(+) T(h)1 cells on day 21 in the mediastinal lymph node but not in the lung. IL-10 was partially involved in the suppression of T(h)1 induction in the lung because pretreatment of mice with anti-IL-10 antibody resulted in increase of P25 TCR-Tg CD4(+) T(h)1 cells in the Mtb-infected lung on day 21 of the infection, whereas neutralization of transforming growth factor-beta, another important suppressive cytokine in the lung, showed no effects on the T(h)1 induction. Our data suggest that induction of anti-mycobacterial CD4(+) T(h)1 cells is suppressed in the mycobacteria-infected lung partially by IL-10.
authors.affiliation: Molecular Microbiology Group, Department of Tropical Infectious Diseases, Center of Molecular Biosciences, Tropical Biosphere Research Center, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Yahagi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Umemura
authors.forename: Toshiki
authors.initials: T
authors.lastname: Tamura
authors.forename: Ai
authors.initials: A
authors.lastname: Kariyone
authors.forename: M Dilara
authors.initials: MD
authors.lastname: Begum
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Hamada
authors.forename: Kiyotetsu
authors.initials: K
authors.lastname: Oshiro
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Kohama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Arakawa
authors.forename: Naoya
authors.initials: N
authors.lastname: Ohara
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation; D016753:Interleukin-10 / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D037182:T-Cell Antigen Receptor Specificity; D018417:Th1 Cells / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10; C072681:Mycobacterium tuberculosis antigens