Expression of memory immunity in the lung following re-exposure to Mycobacterium tuberculosis.
OBJECTIVE
To examine the memory immunity expressed in the lung in response to a low-dose aerosol challenge.


METHODS
Memory-immune C57BL/6 mice were generated by infection followed by drug treatment with isoniazid and rifabutin. Both memory-immune and naive mice were then rechallenged via both the aerosol and intravenous routes. The growth of bacteria in target organs, the expression of cytokines within these organs and the ability of T cells to recognize selected mycobacterial protein antigens were determined over time.


RESULTS
There was a finite delay before immunity was expressed in the lungs of the memory-immune mice. This was in contrast to the immediate control of bacterial growth seen in the liver of intravenously challenged mice. In both cases, the expression of interferon-gamma (IFN-gamma) mRNA in the target organ correlated with the control of bacterial growth. Memory immunity in the spleen and lung differed: whereas splenic T cells strongly recognized the major Ag85 protein, the 45 kDa protein, and a synthetic peptide representing the ESAT molecule, only the Ag85 molecule was recognized by T cells harvested from thoracic lymph nodes after pulmonary rechallenge.


CONCLUSIONS
Immunity, as mediated by IFN-gamma, is expressed more slowly following an aerosol rechallenge and appears to be restricted in terms of antigen specificity. Moreover, very strong levels of memory immunity can prevent progressive disease in the lungs, but cannot prevent the establishment of secondary infection.
Department of Microbiology, Colorado State University, Fort Collins 80523, USA.
A M
AM
Cooper
J E
JE
Callahan
M
M
Keen
J T
JT
Belisle
I M
IM
Orme
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
D012333:RNA, Messenger; D007371:Interferon-gamma