title: Florid pulmonary inflammatory responses in mice vaccinated with Antigen-85 pulsed dendritic cells and challenged by aerosol with Mycobacterium tuberculosis.
abstract: Mice immunized by the intranasal route with dendritic cells harvested from the lungs and then pulsed with Ag85 (LDC-Ag85) were able to prime naive CD4(+) T cells in vivo. As a result splenic CD4(+) T cells from these immunized mice were able to produce IFNgamma following culture with Mycobacterium tuberculosis-infected antigen presenting cells. Hematoxylin and eosin stained lung sections from LDC-Ag85 immunized mice after they had been exposed to aerosol challenge with M. tuberculosis showed a florid infiltration of macrophages and lymphocytes into granulomas and parenchymal tissues when compared to lung sections from control groups implanted with dendritic cells pulsed with ovalbumin. In addition, using immunohistochemistry, these tissues appeared to have more CD4(+) and CD8(+) cells than the control groups. This was confirmed by flow cytometric analysis which showed that lung cell digests contained increased numbers of CD4 and CD8 interferongamma secreting cells. Despite this increase however, no evidence was seen that indicated that the LDC-Ag85 immunized mice were more resistant to M. tuberculosis infection than mice immunized with LDC pulsed with an irrelevant protein. Instead, the potent inflammatory response in the LDC-Ag85 resulted in serious consolidation of the lung tissue.
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Pathology and Immunology, Colorado State University, Fort Collins, CO 80523, USA. malba@lamar.colostate.edu
authors.forename: Mercedes
authors.initials: M
authors.lastname: González-Juarrero
authors.forename: Joanne
authors.initials: J
authors.lastname: Turner
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Basaraba
authors.forename: John T
authors.initials: JT
authors.lastname: Belisle
authors.forename: Ian M
authors.initials: IM
authors.lastname: Orme
mesh_terms: D000217:Acyltransferases / Q000276:immunology*; D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins; D001428:Bacterial Vaccines / Q000276:immunology / Q000633:toxicity*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D015769:Granuloma, Respiratory Tract / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D014611:Vaccination / Q000009:adverse effects*
chemical_list: D000336:Aerosols; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma; D010047:Ovalbumin; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis; C121433:antigen 85B, Mycobacterium tuberculosis; C119774:antigen 85C, Mycobacterium tuberculosis