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J Immunol ; 168(6): 2773-81, 2002 Mar 15.
Article in English | MEDLINE | ID: mdl-11884445

ABSTRACT

Protection against infection with pneumococci is provided by anti-capsular polysaccharide (caps-PS) Abs. We investigated whether CD40 ligand (CD40L) plays a role in T lymphocyte-mediated regulation of the immune response to caps-PS, which are considered thymus-independent Ags. Administration of MR1, an antagonist mAb against murine CD40L, in BALB/c mice immunized with Pneumovax resulted in an inhibition of the IgM and IgG Ab response for various caps-PS serotypes. Evidence for the involvement of CD4(+) T lymphocytes in the Ab response to caps-PS was obtained in SCID/SCID mice that, when reconstituted with B lymphocytes and CD4(+) T lymphocytes, mounted a higher specific IgM response compared with SCID/SCID mice reconstituted with only B lymphocytes. This helper effect of CD4(+) T lymphocytes was abrogated by MR1. Blocking CD40L in vitro decreased the IgM response to caps-PS and abolished the helper effect of CD4(+) T lymphocytes. CD8(+) T lymphocyte-depleted murine spleen cells mounted a higher in vivo immune response than total murine spleen cells, which provided evidence for a suppressive role of CD8(+) T lymphocytes on the anti-caps-PS immune response. CD4(+) T lymphocyte-depleted murine spleen cells, leaving a B and CD8(+) T lymphocyte fraction, elicited only a weak in vivo and in vitro Ab response, which was enhanced after MR1 administration. In summary, our data provide evidence that T lymphocytes contribute to the regulation of the anti-caps-PS immune response in a CD40L-dependent manner.


Subject(s)
CD40 Ligand/physiology , Polysaccharides, Bacterial/immunology , Streptococcus pneumoniae/immunology , T-Lymphocyte Subsets/immunology , Animals , Antibodies, Bacterial/biosynthesis , Antibodies, Blocking/administration & dosage , Bacterial Capsules , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/microbiology , CD40 Ligand/immunology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/microbiology , Cells, Cultured , Immunoglobulin M/biosynthesis , Injections, Intraperitoneal , Mice , Mice, Inbred BALB C , Mice, SCID , Pneumococcal Vaccines/administration & dosage , Pneumococcal Vaccines/immunology , Polysaccharides, Bacterial/administration & dosage , T-Lymphocyte Subsets/microbiology , T-Lymphocytes, Regulatory/immunology
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