Modulation of naive CD4+ T-cell responses to an airway antigen during pulmonary mycobacterial infection.
During pulmonary mycobacterial infection, there is increased trafficking of dendritic cells from the lungs to the draining lymph nodes. We hypothesized that ongoing mycobacterial infection would modulate recruitment and activation of antigen-specific naive CD4+ T cells after airway antigen challenge. BALB/c mice were infected by aerosol with Mycobacterium bovis BCG. At peak bacterial burden in the lungs (4 to 6 weeks postinfection), carboxy-fluorescein diacetate succinimidyl ester-labeled naive ovalbumin-specific DO11.10 T cells were adoptively transferred into infected and uninfected mice. Recipient mice were challenged intranasally with soluble ovalbumin (OVA), and OVA-specific T-cell responses were measured in the lungs, draining mediastinal lymph nodes (MLN), and spleens. OVA challenge resulted in increased activation and proliferation of OVA-specific T cells in the draining MLN of both infected and uninfected mice. However, only BCG-infected mice had prominent OVA-specific T-cell activation, proliferation, and Th1 differentiation in the lungs. BCG infection caused greater distribution of airway OVA to pulmonary dendritic cells and enhanced presentation of OVA peptide by lung CD11c+ cells. Together, these data suggest that an existing pulmonary mycobacterial infection alters the phenotype of lung dendritic cells so that they can activate antigen-specific naive CD4+ T cells in the lungs in response to airway antigen challenge.
Anis
Mursalin M
MM
Department of Pathology, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-4984, USA.
Fulton
Scott A
SA
Reba
Scott M
SM
Harding
Clifford V
CV
Boom
W Henry
WH
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D039521:CD11c Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008482:Mediastinum; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000472:pathogenicity*; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology
D000941:Antigens; D039521:CD11c Antigen; D010047:Ovalbumin