title: CD4-T-lymphocyte interactions with pneumolysin and pneumococci suggest a crucial protective role in the host response to pneumococcal infection.
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.
authors.affiliation: Department of Infection, Immunity & Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom. ak13@le.ac.uk
authors.forename: Aras
authors.initials: A
authors.lastname: Kadioglu
authors.forename: William
authors.initials: W
authors.lastname: Coward
authors.forename: M Joseph
authors.initials: MJ
authors.lastname: Colston
authors.forename: Colin R A
authors.initials: CR
authors.lastname: Hewitt
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D005260:Female; D005802:Genes, MHC Class II; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D011008:Pneumococcal Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D013301:Streptolysins / Q000235:genetics / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D015847:Interleukin-4; D007371:Interferon-gamma