Modulation of Naive CD4+ T-Cell Responses to an Airway Antigen during Pulmonary Mycobacterial Infection

Department of Pathology, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-4984, USA.
Infection and Immunity (Impact Factor: 3.73). 06/2007; 75(5):2260-8. DOI: 10.1128/IAI.01709-06
Source: PubMed


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.

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