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https://hdl.handle.net/2440/54087
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DC Field | Value | Language |
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dc.contributor.author | Chen, Q. | - |
dc.contributor.author | Cannons, J. | - |
dc.contributor.author | Paton, J. | - |
dc.contributor.author | Akiba, H. | - |
dc.contributor.author | Schwartzberg, P. | - |
dc.contributor.author | Snapper, C. | - |
dc.date.issued | 2008 | - |
dc.identifier.citation | Journal of Immunology, 2008; 181(12):8258-8266 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.issn | 1550-6606 | - |
dc.identifier.uri | http://hdl.handle.net/2440/54087 | - |
dc.description.abstract | Polysaccharide (PS)- and protein-specific murine IgG responses to intact Streptococcus pneumoniae (Pn) are both dependent on CD4(+) T cell help, B7-dependent costimulation, and CD40/CD40 ligand interactions. However, the primary PS-specific, relative to protein-specific, IgG response terminates more rapidly, requires a shorter period of T cell help and B7-dependent costimulation, and fails to generate memory. In light of the critical role for ICOS/ICOS ligand interactions in sustaining T cell-dependent Ig responses and promoting germinal center reactions, we hypothesized that this interaction was nonessential for PS-specific IgG responses to Pn. We now demonstrate that ICOS(-/-), relative to wild-type, mice elicit a normal PS-specific IgG isotype response to Pn, despite marked inhibition of both the primary and secondary IgG anti-protein (i.e., PspA, PspC, and PsaA) response. A blocking anti-ICOS ligand mAb injected during primary Pn immunization inhibits both the primary anti-protein response and the generation of protein-specific memory, but has no effect when injected during secondary immunization. In contrast to Pn, both PS- and protein-specific IgG responses to a pneumococcal conjugate vaccine are inhibited in ICOS(-/-) mice. ICOS(-/-) mice immunized with intact Pn or conjugate exhibit nearly complete abrogation in germinal center formation. Finally, although mice that lack the adaptor molecule SAP (SLAM-associated protein) resemble ICOS(-/-) mice (and can exhibit decreased ICOS expression), we observe that the PS-specific, as well as protein-specific, IgG responses to both Pn and conjugate are markedly defective in SAP(-/-) mice. These data define a novel T cell-, SAP-, and B7-dependent, but ICOS-independent, extrafollicular pathway of Ig induction. | - |
dc.description.statementofresponsibility | Quanyi Chen, Jennifer L. Cannons, James C. Paton, Hisaya Akiba, Pamela L. Schwartzberg, and Clifford M. Snapper | - |
dc.language.iso | en | - |
dc.publisher | Amer Assoc Immunologists | - |
dc.source.uri | http://www.jimmunol.org/cgi/content/full/181/12/8258 | - |
dc.subject | CD4-Positive T-Lymphocytes | - |
dc.subject | Animals | - |
dc.subject | Mice, Inbred BALB C | - |
dc.subject | Mice, Inbred C57BL | - |
dc.subject | Mice, Transgenic | - |
dc.subject | Mice, Knockout | - |
dc.subject | Mice | - |
dc.subject | Streptococcus pneumoniae | - |
dc.subject | Phosphorylcholine | - |
dc.subject | Bacterial Capsules | - |
dc.subject | Intracellular Signaling Peptides and Proteins | - |
dc.subject | Bacterial Proteins | - |
dc.subject | Antigens, Differentiation, T-Lymphocyte | - |
dc.subject | Streptococcal Vaccines | - |
dc.subject | Vaccines, Conjugate | - |
dc.subject | Antibodies, Bacterial | - |
dc.subject | Binding Sites, Antibody | - |
dc.subject | Epitopes, T-Lymphocyte | - |
dc.subject | Signal Transduction | - |
dc.subject | Female | - |
dc.subject | Inducible T-Cell Co-Stimulator Protein | - |
dc.subject | Signaling Lymphocytic Activation Molecule Associated Protein | - |
dc.subject | CD28 Antigens | - |
dc.title | A Novel ICOS-Independent, but CD28- and SAP-Dependent, Pathway of T Cell-Dependent, Polysaccharide-Specific Humoral Immunity in Response to Intact Streptococcus pneumoniae versus Pneumococcal Conjugate Vaccine | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.4049/jimmunol.181.12.8258 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Paton, J. [0000-0001-9807-5278] | - |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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