Pulmonary immune responses during primary @entity2497 - Calmette-Guerin bacillus infection in C57Bl/6 XXXX .

@entity39 @entity19 @entity3794 @entity281 @entity358 @entity2499 @entity2497
Mechanisms of protective immunity to @entity281 in the lung remain poorly defined. In this study, T-cell subset expansion and cytokine expression in bronchoalveolar spaces, lung parenchyma, and mediastinal lymph nodes of @entity19 infected intratracheally with @entity2497 -Calmette-Guerin bacillus (BCG) were analyzed in parallel with histopathology and bacterial burden. @entity2499 -BCG was cleared rapidly from bronchoalveolar spaces without evidence for persistence. In lung parenchyma bacteria grew during the first 4 wk followed by gradual clearance with less than 0.1% of the original inoculum persisting for more than 8 mo. Clearance of @entity2499 -BCG from bronchoalveolar lavage was associated with recruitment of both neutrophils and lymphocytes. Lung CD4(+), CD8(+), and gammadelta T-cell receptor-positive T cells expanded maximally by Week 4, and declined by Week 8 to control values despite bacterial persistence. Both CD4(+) and CD8(+) lung T cells produced interferon (IFN)-gamma in response to @entity2499 -BCG. Four distinct pathologic states of lung parenchymal infection were noted. Early focal sub-bronchial inflammation with transmigration of cells into airways was followed by diffuse peribronchitis, perivasculitis, and @entity3794 with activated macrophages, lymphoblasts, and occasional giant cells. The latter stage corresponded to maximal @entity2499 -BCG growth. @entity281 consisted of small lymphocytes and foamy macrophages, which coincided with decreasing @entity2499 -BCG colony-forming units, T-cell infiltration, and IFN-gamma expression. A final quiescent phase consisted of residual lymphoid aggregates and perivasculitis associated with persistent spontaneous IFN-gamma production. Bacterial dissemination to lymph node and spleen occurred by Week 4 and declined in parallel to lung. In contrast to lung, IFN-gamma secretion was detected only late despite early expansion of CD4(+) and CD8(+) T cells. By reverse transcriptase/polymerase chain reaction, IFN-gamma and interleukin (IL)-12 p40 messenger RNA (mRNA) in lung paralleled IFN-gamma protein production. Tumor @entity39 factor-alpha, IL-4 and IL-10 mRNA expression was not increased during @entity2499 -BCG @entity358 . Thus, protective immunity to @entity2499 -BCG in the lung evolved differently in air space, lung, and lymph node.
