Kinetics of changes in lymphocyte sub-populations in mouse lungs after intrapulmonary infection with M. bovis (Bacillus Calmette-Guerin) and identity of cells responsible for IFNgamma responses.
Gamma interferon (IFNgamma) plays a key role in host defense against pulmonary mycobacterial infections. A variety of lymphocyte subsets may participate in producing pulmonary IFNgamma responses, but their relative contributions after mycobacterial infection have not been clearly elucidated. To address this question, C57Bl/6 female mice were infected by intrapulmonary instillation of 2.5 x 104 BCG (Mycobacterium bovis Bacillus Calmette-Guerin). Lymphocyte populations in lung interstitium were examined at different time points after the infection. BCG load in lungs peaked between 4 and 6 weeks post-infection and declined to very low levels by the 12th week of infection. Recovery of lung interstitial lymphocytes doubled by 4-6 weeks after infection and declined thereafter. Flow cytometric analysis of the lung-derived lymphocytes revealed that about 5% of the these cells made IFNgamma in control mice, and this baseline IFNgamma production involved T (CD3+NK1.1-), NK (CD3-NK1.1+) and NKT (CD3+NK1.1+) cells. As the BCG lung infection peaked, the total number of CD3+ T cells in the lungs increased threefold at 5-6 weeks post-infection. There was a marked increase (sixfold) in the number of T cells secreting IFNgamma 5-6 weeks post-infection. Some increase was also noted in the NKT cells making IFNgamma, but the numbers of NK cells making IFNgamma in BCG-infected lungs remained unaltered. Our results suggest that whereas NK and NKT cells contribute to baseline IFNgamma secretion in control lungs, expansion in the IFNgamma-producing T-cell population was essentially responsible for the augmented response seen in lungs of BCG-infected mice.
Saxena
R K
RK
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Weissman
D
D
Saxena
Q B
QB
Simpson
J
J
Lewis
D M
DM
D000818:Animals; D001402:B-Lymphocytes / Q000145:classification / Q000166:cytology / Q000276:immunology; D005260:Female; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000145:classification / Q000166:cytology / Q000276:immunology; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000276:immunology*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000145:classification* / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology*; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
D007371:Interferon-gamma