Abstract
Previously, we had shown that T cells accumulated in peribronchiolar and perivascular areas of lungs soon after intranasal infection with Streptococcus pneumoniae. We have now presented new evidence, using major histocompatibility class II-deficient mice, that CD4 cells are important for early protective immunity. In addition, we have also shown that a population of human CD4 cells migrates towards pneumococci and that in vivo-passaged pneumococci are substantially more potent at inducing migration than in vitro-grown bacteria. This migratory process is unique to a specific population of CD4 cells, is highly reproducible, and is independent of prior CD4 cell activation, and yet the migratory process results in a significant proportion of CD4 cells becoming activated. The production of pneumolysin is a key facet in the induction of migration of CD4 cells by in vivo bacteria, as pneumolysin-deficient bacteria do not induce migration, but the data also show that pneumolysin alone is not sufficient to explain the enhanced migration. Increased CD25 expression occurs during migration, and a higher percentage of cells in the migrated population express gamma interferon or interleukin 4 (IL-4) than in the population that did not migrate. There is evidence that the activation of IL-4 expression occurs during migration.
Highlights
The pneumococcus is an important human pathogen that colonizes the upper respiratory tract, eventually leading to diseases of high morbidity and mortality such as pneumonia, septicemia, and meningitis
In order to investigate whether or not CD4ϩ T cells had any effect upon pneumococcal infection, major histocompatibility complex class II (MHC-II) knockout (A0/0) mice were used in a study of pneumonia and septicemia
It has been demonstrated previously that T cells migrated over time to areas of heavy pneumococcal invasion, to peribronchiolar and perivascular areas rich in pneumolysin production [7, 18]
Summary
The pneumococcus is an important human pathogen that colonizes the upper respiratory tract, eventually leading to diseases of high morbidity and mortality such as pneumonia, septicemia, and meningitis. Antibodies to pneumolysin have been shown to inhibit the virulence of wild-type strains, and pneumolysin-deficient strains are complemented by coinfection with wild-type strains, suggesting that pneumolysin is required for successful bacterial virulence [2, 3, 23] It has been shown with a mouse model of bronchopneumonia that the virulence of a pneumolysin-deficient pneumococcus was significantly reduced, with low growth of bacteria in the lungs and reduced development of the cellular inflammatory response compared to pneumolysin-sufficient pneumococci [18]. Infection, and the fact that T cells are an important component of the inflammatory host immune response to the pneumococcal toxin pneumolysin, has been shown [18]. It was verified that both the cytolytic and complementactivating activities of pneumolysin contribute to the influx of inflammatory cells but that the toxin’s complement-activating activity was more important for the recruitment of T cells to inflammatory lesions than for its pore-forming activity [17]
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