Low CD4 T cell immunity to pneumolysin is associated with nasopharyngeal carriage of pneumococci in children

Background. Recent studies in mice have suggested that T cell immunity may be protective against pneumococcal infection. Methods. CD4 T cell proliferative responses to the pneumococcal proteins pneumolysin (Ply), Ply toxoid (F433), and choline-binding protein A were investigated in peripheral blood mononuclear cells (PBMCs) and adenoidal mononuclear cells (MNCs) obtained from children undergoing adenoidectomy. Results. Ply and F433 induce significant proliferation of CD4 T cells in both PBMCs and adenoidal MNCs, and both memory and naive phenotypes of CD4 T cells proliferated after stimulation. In PBMCs, CD4 T cell proliferation induced by Ply and F433, which was associated with increased production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, was significantly lower in children who were culture positive for pneumococcus than in those who were culture negative for pneumococcus (P <.05). Between groups, no such difference was observed in adenoidal MNC CD4 T cell proliferation, which was associated with production of IFN-gamma and interleukin (IL)-10. The CD4 T cell proliferation induced by Ply and F433 was inhibited by antibodies to Toll-like receptor 4. Conclusion. These data suggest that Ply induces CD4 T cell proliferative responses with production of IFN-gamma and TNF-alpha in PBMCs or of IFN-gamma and IL-10 in adenoidal MNCs, which may be important in modulating pneumococcal carriage in children.