Essential role for CD40 ligand interactions in T lymphocyte-mediated modulation of the murine immune response to pneumococcal capsular polysaccharides.
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.
Jeurissen
Axel
A
Department of Molecular Cell Biology, Laboratory of Experimental Laboratory Medicine, Catholic University Leuven, Leuven, Belgium.
Wuyts
Margreet
M
Kasran
Ahmad
A
Ramdien-Murli
Sheema
S
Boon
Louis
L
Ceuppens
Jan L
JL
Bossuyt
Xavier
X
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D019138:Antibodies, Blocking / Q000008:administration & dosage; D016667:Bacterial Capsules; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D023201:CD40 Ligand / Q000276:immunology / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D007075:Immunoglobulin M / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000907:Antibodies, Bacterial; D019138:Antibodies, Blocking; D007075:Immunoglobulin M; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; C116177:capsular polysaccharide 19F; C413446:type 3 capsular polysaccharide, Streptococcus pneumoniae; D023201:CD40 Ligand