Interactions between T cells responding to concurrent mycobacterial and influenza infections.
CD4(+) T cells are central in mediating granuloma formation and limiting growth and dissemination of mycobacterial infections. To determine whether T cells responding to influenza infection can interact with T cells responding to Mycobacterium bovis bacille Calmette-Guérin (BCG) infection and disrupt granuloma formation, we infected mice containing two monoclonal T cell populations specific for the model Ags pigeon cytochrome c (PCC) and hen egg lysozyme (HEL). These mice were chronically infected with PCC epitope-tagged BCG (PCC-BCG) and acutely infected with HEL epitope-tagged influenza virus (HEL-flu). In these mice, PCC-BCG infection is much more abundant in the liver than the lung, whereas HEL-flu infection is localized to the lung. We observe that both T cells have access to both inflammatory sites, but that PCC-specific T cells dominate the PCC-BCG inflammatory site in the liver, whereas HEL-specific T cells dominate the HEL-flu inflammatory site in the lung. Influenza infection, in the absence of an influenza-specific T cell response, is able to increase the activation state and IFN-gamma secretion of PCC-BCG-specific T cells in the granuloma. Activation of HEL-specific T cells allows them to secrete IFN-gamma and contribute to protection in the granuloma. Ultimately, infection with influenza has little effect on bacterial load, and bacteria do not disseminate. In summary, these data illustrate complex interactions between T cell responses to infectious agents that can affect effector responses to pathogens.
Co
Dominic O
DO
Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, School of Veterinary Medicine, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
Hogan
Laura H
LH
Karman
Jozsef
J
Heninger
Erika
E
Vang
Shoua
S
Wells
Krisna
K
Kawaoka
Yoshihiro
Y
Sandor
Matyas
M
D000818:Animals; D000941:Antigens / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002645:Chickens; D002999:Clone Cells; D010856:Columbidae; D045304:Cytochromes c / Q000276:immunology; D006099:Granuloma / Q000209:etiology / Q000276:immunology; D006801:Humans; D007109:Immunity; D007251:Influenza, Human / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009113:Muramidase / Q000276:immunology; D009163:Mycobacterium bovis; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology
D000941:Antigens; D045304:Cytochromes c; D009113:Muramidase