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https://hdl.handle.net/2440/54087
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Type: | Journal article |
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 |
Author: | Chen, Q. Cannons, J. Paton, J. Akiba, H. Schwartzberg, P. Snapper, C. |
Citation: | Journal of Immunology, 2008; 181(12):8258-8266 |
Publisher: | Amer Assoc Immunologists |
Issue Date: | 2008 |
ISSN: | 0022-1767 1550-6606 |
Statement of Responsibility: | Quanyi Chen, Jennifer L. Cannons, James C. Paton, Hisaya Akiba, Pamela L. Schwartzberg, and Clifford M. Snapper |
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. |
Keywords: | CD4-Positive T-Lymphocytes Animals Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic Mice, Knockout Mice Streptococcus pneumoniae Phosphorylcholine Bacterial Capsules Intracellular Signaling Peptides and Proteins Bacterial Proteins Antigens, Differentiation, T-Lymphocyte Streptococcal Vaccines Vaccines, Conjugate Antibodies, Bacterial Binding Sites, Antibody Epitopes, T-Lymphocyte Signal Transduction Female Inducible T-Cell Co-Stimulator Protein Signaling Lymphocytic Activation Molecule Associated Protein CD28 Antigens |
DOI: | 10.4049/jimmunol.181.12.8258 |
Published version: | http://www.jimmunol.org/cgi/content/full/181/12/8258 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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