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CD4-T-Lymphocyte Interactions with Pneumolysin and Pneumococci Suggest a Crucial Protective Role in the Host Response to Pneumococcal Infection

Aras Kadioglu,^1* William Coward,¹ M. Joseph Colston,^2, Colin R. A. Hewitt,¹ and Peter W. Andrew¹

Department of Infection, Immunity & Inflammation, University of Leicester, Leicester LE1 9HN,¹ Division of Mycobacterial Research, National Institute for Medical Research, London NW7 1AA, United Kingdom²

Received 5 August 2003/ Returned for modification 29 September 2003/ Accepted 23 January 2004

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.

Editor: J. N. Weiser

Tragically, Jo Colston died during the preparation of the manuscript.

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