title: Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs.
abstract: The onset of the adaptive immune response to Mycobacterium tuberculosis is delayed compared with that of other infections or immunization, and allows the bacterial population in the lungs to expand markedly during the preimmune phase of infection. We used adoptive transfer of M. tuberculosis Ag85B-specific CD4(+) T cells to determine that the delayed adaptive response is caused by a delay in initial activation of CD4(+) T cells, which occurs earliest in the local lung-draining mediastinal lymph node. We also found that initial activation of Ag85B-specific T cells depends on production of antigen by bacteria in the lymph node, despite the presence of 100-fold more bacteria in the lungs. Although dendritic cells have been found to transport M. tuberculosis from the lungs to the local lymph node, airway administration of LPS did not accelerate transport of bacteria to the lymph node and did not accelerate activation of Ag85B-specific T cells. These results indicate that delayed initial activation of CD4(+) T cells in tuberculosis is caused by the presence of the bacteria in a compartment that cannot be mobilized from the lungs to the lymph node, where initial T cell activation occurs.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Wolf
authors.forename: Ludovic
authors.initials: L
authors.lastname: Desvignes
authors.forename: Beth
authors.initials: B
authors.lastname: Linas
authors.forename: Niaz
authors.initials: N
authors.lastname: Banaiee
authors.forename: Toshiki
authors.initials: T
authors.lastname: Tamura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.forename: Joel D
authors.initials: JD
authors.lastname: Ernst
mesh_terms: D000217:Acyltransferases / Q000737:chemistry*; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000378:metabolism; D007107:Immune System / Q000473:pathology*; D008168:Lung / Q000382:microbiology*; D008198:Lymph Nodes / Q000473:pathology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis