The human antibody response to pneumococcal capsular polysaccharides is dependent on the CD40-CD40 ligand interaction.
Protection against infections with Streptococcus pneumoniae is mediated by antibodies against the capsular polysaccharides (caps-PS). Here we show that in in vitro experiments CD4+ T lymphocytes stimulate and CD8+ T lymphocytes inhibit the human anti-caps-PS antibody response. Using antagonistic anti-CD40 and antagonistic anti-CD40 ligand (CD40L) monoclonal antibodies, we showed that the CD4+ T lymphocyte-mediated stimulation is dependent on the CD40-CD40L interaction. The role of CD40L was further illustrated by the observation that CD4+ T lymphocytes obtained from a patient with hyper-IgM syndrome were unable to enhance the immune response to caps-PS. Furthermore, CD4+ T lymphocytes from cord blood, which did not express CD40L in response to stimulation with caps-PS, failed to stimulate the antibody response of adult B lymphocytes to caps-PS. These in vitro findings were confirmed by in vivo experiments in which SCID/SCID mice were reconstituted with human mononuclear cells. Furthermore, we showed that caps-PS induce production of IL-4, IL-6, IL-10, and IFN-gamma, and that this enhanced production was inhibited by blocking the CD40-CD40L interaction. This is the first demonstration that the human immune response to caps-PS, which is markedly regulated by T lymphocytes, is dependent on the CD40-CD40L interaction.
Experimental Laboratory Medicine, Department of Molecular Cell Biology, Faculty of Medicine, Catholic University Leuven, Leuven, Belgium.
Axel
A
Jeurissen
Experimental Laboratory Medicine, Department of Molecular Cell Biology, Faculty of Medicine, Catholic University Leuven, Leuven, Belgium.
Greet
G
Wuyts
Laboratory of Experimental Immunology, Department of Pathophysiology, Faculty of Medicine, Catholic University Leuven, Leuven, Belgium.
Ahmad
A
Kasran
MacroZyme, B.V., Amsterdam, The Netherlands.
Seema
S
Ramdien-Murli
Experimental Laboratory Medicine, Department of Molecular Cell Biology, Faculty of Medicine, Catholic University Leuven, Leuven, Belgium.
Norbert
N
Blanckaert
MacroZyme, B.V., Amsterdam, The Netherlands.
Louis
L
Boon
Laboratory of Experimental Immunology, Department of Pathophysiology, Faculty of Medicine, Catholic University Leuven, Leuven, Belgium.
Jan L
JL
Ceuppens
Experimental Laboratory Medicine, Department of Molecular Cell Biology, Faculty of Medicine, Catholic University Leuven, Leuven, Belgium.
Xavier
X
Bossuyt
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000097:blood; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D006942:Hypergammaglobulinemia / Q000276:immunology; D007075:Immunoglobulin M; D008211:Lymphocyte Cooperation; D051379:Mice; D016513:Mice, SCID; D013296:Streptococcus pneumoniae / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D019013:CD40 Antigens; D016207:Cytokines; D007075:Immunoglobulin M; D023201:CD40 Ligand