title: CD4+ T lymphocytes expressing CD40 ligand help the IgM antibody response to soluble pneumococcal polysaccharides via an intermediate cell type.
abstract: Streptococcus pneumoniae causes serious infections in children, the elderly, and immunocompromised patients. Protection against infections with S. pneumoniae is mediated through Abs against the capsular polysaccharides (caps-PS). We previously showed that the murine Ab response to caps-PS is dependent on CD40-CD40L interaction. In the present paper, we addressed the question of whether the CD40-CD40L-mediated modulation of the anti-caps-PS immune reaction is the result of a direct interaction between B lymphocytes and T lymphocytes or of an indirect interaction. SCID/SCID mice reconstituted with B lymphocytes from wild-type mice did not mount anti-caps-PS Abs. SCID/SCID mice reconstituted with B lymphocytes from wild-type mice and CD4+ T lymphocytes from wild-type mice but not CD4+ T lymphocytes from CD40L knockout mice stimulated the anti-caps-PS Ab response. This indicated that CD4+ T lymphocytes stimulated the anti-caps-PS Ab response in a CD40L-dependent manner. SCID/SCID mice reconstituted with B lymphocytes from CD40 knockout mice and CD4+ T lymphocytes from wild-type mice generated an anti-caps-PS Ab response that could be inhibited by MR1, a blocking anti-CD40L Ab. These data indicated that CD4+ T lymphocytes stimulated the anti-caps-PS Ab response in an indirect way. Finally, lethally irradiated CD40 knockout mice reconstituted with bone marrow from wild-type mice mounted an anti-caps-PS Ab response that was comparable to the Ab response in wild-type mice, revealing that the required CD40 was on hemopoietic cells. In conclusion, we provide evidence that CD4+ T lymphocytes expressing CD40L stimulate the Ab response to soluble caps-PS by interacting with CD40-expressing non-B cells.
authors.affiliation: Laboratory of Experimental Laboratory Medicine, Department of Medical Diagnostic Sciences, Catholic University, Leuven Belgium.
authors.forename: Axel
authors.initials: A
authors.lastname: Jeurissen
authors.forename: An D
authors.initials: AD
authors.lastname: Billiau
authors.forename: Leen
authors.initials: L
authors.lastname: Moens
authors.forename: Li
authors.initials: L
authors.lastname: Shengqiao
authors.forename: Willy
authors.initials: W
authors.lastname: Landuyt
authors.forename: Greet
authors.initials: G
authors.lastname: Wuyts
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Mark
authors.initials: M
authors.lastname: Waer
authors.forename: Jan L
authors.initials: JL
authors.lastname: Ceuppens
authors.forename: Xavier
authors.initials: X
authors.lastname: Bossuyt
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D007075:Immunoglobulin M; D023201:CD40 Ligand