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Infection and Immunity, August 2006, p. 4735-4743, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00165-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Regulation of Production of Mucosal Antibody to Pneumococcal Protein Antigens by T-Cell-Derived Gamma Interferon and Interleukin-10 in Children

Department of Clinical Sciences at South Bristol, Academic Unit of Child Health, University of Bristol, Bristol, United Kingdom,¹ School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia,² Division of Infection & Immunity, University of Glasgow, Glasgow, United Kingdom,³ Research Center for Infectious Diseases, University of Wuerzburg, Wuerzburg, Germany,⁴ Department of Otolaryngology, North Bristol NHS Trust, Southmead Hospital, University of Bristol, Bristol, United Kingdom⁵

Received 31 January 2006/ Returned for modification 13 April 2006/ Accepted 10 May 2006

Nasopharyngeal tonsils (adenoids) are part of human nasopharynx-associated lymphoid tissue, which may play an important role in local defense against pneumococci. Recent studies with animals have suggested that several pneumococcal proteins, including CbpA and pneumolysin (Ply), may be vaccine candidates. Our recent data obtained with children suggest that antibodies to these proteins may protect against carriage. This study was performed to investigate the regulation of the T-cell-dependent antibody responses to CbpA and pneumolysin by cytokines in adenoidal immune cells from children. Adenoidal mononuclear cells (MNC) were cultured with pneumococcal concentrated culture supernatants (CCS) or recombinant proteins. Cytokine expression profiles in adenoidal MNC after antigen stimulation were analyzed by reverse transcription-PCR, protein array analysis, and an immunoassay, along with an antibody production analysis. The roles, interactions, and cellular sources of the main cytokines identified were evaluated further. Pneumococcal CCS induced production of CbpA- and Ply-specific antibodies in association with several chemokines and cytokines, including gamma interferon (IFN-) and interleukin-10 (IL-10) in MNC. The antibody production correlated well with the concentrations of these two cytokines. Addition of recombinant IFN- or IL-10 enhanced antibody production, and monoclonal antibodies to these two cytokines and T-cell depletion significantly reduced antibody production. Intracellular cytokine staining showed that T cells are a major source of IFN- and IL-10. Recombinant Ply and, to a lesser extent, recombinant CbpA induced significant production of IFN- and IL-10 in MNC. T-cell-derived IFN- and IL-10 may be key regulators of production of mucosal antibody to pneumococcal protein antigens in the nasopharynx and may play an important role in local protection against pneumococcal infection in children.

Editor: J. N. Weiser

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