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4-1BB (CD137) differentially regulates murine in vivo protein- and polysaccharide-specific immunoglobulin isotype responses to Streptococcus pneumoniae.
Infect Immun. 2003 Jan; 71(1):196-204.II

Abstract

4-1BB (CD137) is induced on activated CD4(+) and CD8(+) T cells and delivers a costimulatory signal upon binding the 4-1BB ligand (4-1BBL) expressed on antigen-presenting cells. Induction of 4-1BB is dependent on activation via the T-cell receptor (TCR) and possibly CD28. It was previously demonstrated that both an in vivo protein (pneumococcal surface protein A [PspA])- and polysaccharide (phosphorylcholine [PC] determinant of teichoic acid)-specific immunoglobulin (Ig) isotype response to Streptococcus pneumoniae was dependent on CD4(+) TCRalphabeta(+) T cells and B7-dependent costimulation through CD28. We thus postulated that 4-1BB costimulation would also play a role in regulating the in vivo anti-PspA and anti-PC response to S. pneumoniae. We demonstrate that mice genetically deficient in 4-1BBL elicit a markedly reduced IgM and IgG anti-PC but normal primary and secondary IgG anti-PspA responses to S. pneumoniae relative to those for wild-type mice. However, injection of an agonistic anti-4-1BB monoclonal antibody (MAb), while having no significant effect on the anti-PC response, strongly inhibits the primary anti-PspA response, the generation of PspA-specific memory, and germinal center formation but does not induce a lasting state of tolerance. In contrast, anti-4-1BB MAb has no effect on the anti-PspA response when injected only at the time of secondary immunization. Delay of the addition of anti-4-1BB leads to progressively less inhibition of the primary response up to day 8. This inhibition is independent of CD8(+) T cells and is associated with the expansion of CD4(+) T cells with an activated phenotype, which is partly dependent on B7-dependent costimulation. These data are the first to suggest a stimulatory role for endogenous 4-1BB-4-1BBL interactions during a humoral immune response to a pathogen and further underscore significant differences in costimulation requirements for an in vivo protein- versus polysaccharide-specific Ig isotype response to an extracellular bacterium.

Authors+Show Affiliations

Department of Pathology. Biomedical Instrumentation Center, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12496166

Citation

Wu, Zheng-Qi, et al. "4-1BB (CD137) Differentially Regulates Murine in Vivo Protein- and Polysaccharide-specific Immunoglobulin Isotype Responses to Streptococcus Pneumoniae." Infection and Immunity, vol. 71, no. 1, 2003, pp. 196-204.
Wu ZQ, Khan AQ, Shen Y, et al. 4-1BB (CD137) differentially regulates murine in vivo protein- and polysaccharide-specific immunoglobulin isotype responses to Streptococcus pneumoniae. Infect Immun. 2003;71(1):196-204.
Wu, Z. Q., Khan, A. Q., Shen, Y., Wolcott, K. M., Dawicki, W., Watts, T. H., Mittler, R. S., & Snapper, C. M. (2003). 4-1BB (CD137) differentially regulates murine in vivo protein- and polysaccharide-specific immunoglobulin isotype responses to Streptococcus pneumoniae. Infection and Immunity, 71(1), 196-204.
Wu ZQ, et al. 4-1BB (CD137) Differentially Regulates Murine in Vivo Protein- and Polysaccharide-specific Immunoglobulin Isotype Responses to Streptococcus Pneumoniae. Infect Immun. 2003;71(1):196-204. PubMed PMID: 12496166.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 4-1BB (CD137) differentially regulates murine in vivo protein- and polysaccharide-specific immunoglobulin isotype responses to Streptococcus pneumoniae. AU - Wu,Zheng-Qi, AU - Khan,Abdul Q, AU - Shen,Yi, AU - Wolcott,Karen M, AU - Dawicki,Wojciech, AU - Watts,Tania H, AU - Mittler,Robert S, AU - Snapper,Clifford M, PY - 2002/12/24/pubmed PY - 2003/2/11/medline PY - 2002/12/24/entrez SP - 196 EP - 204 JF - Infection and immunity JO - Infect. Immun. VL - 71 IS - 1 N2 - 4-1BB (CD137) is induced on activated CD4(+) and CD8(+) T cells and delivers a costimulatory signal upon binding the 4-1BB ligand (4-1BBL) expressed on antigen-presenting cells. Induction of 4-1BB is dependent on activation via the T-cell receptor (TCR) and possibly CD28. It was previously demonstrated that both an in vivo protein (pneumococcal surface protein A [PspA])- and polysaccharide (phosphorylcholine [PC] determinant of teichoic acid)-specific immunoglobulin (Ig) isotype response to Streptococcus pneumoniae was dependent on CD4(+) TCRalphabeta(+) T cells and B7-dependent costimulation through CD28. We thus postulated that 4-1BB costimulation would also play a role in regulating the in vivo anti-PspA and anti-PC response to S. pneumoniae. We demonstrate that mice genetically deficient in 4-1BBL elicit a markedly reduced IgM and IgG anti-PC but normal primary and secondary IgG anti-PspA responses to S. pneumoniae relative to those for wild-type mice. However, injection of an agonistic anti-4-1BB monoclonal antibody (MAb), while having no significant effect on the anti-PC response, strongly inhibits the primary anti-PspA response, the generation of PspA-specific memory, and germinal center formation but does not induce a lasting state of tolerance. In contrast, anti-4-1BB MAb has no effect on the anti-PspA response when injected only at the time of secondary immunization. Delay of the addition of anti-4-1BB leads to progressively less inhibition of the primary response up to day 8. This inhibition is independent of CD8(+) T cells and is associated with the expansion of CD4(+) T cells with an activated phenotype, which is partly dependent on B7-dependent costimulation. These data are the first to suggest a stimulatory role for endogenous 4-1BB-4-1BBL interactions during a humoral immune response to a pathogen and further underscore significant differences in costimulation requirements for an in vivo protein- versus polysaccharide-specific Ig isotype response to an extracellular bacterium. SN - 0019-9567 UR - https://www.unboundmedicine.com/medline/citation/12496166/4_1BB__CD137__differentially_regulates_murine_in_vivo_protein__and_polysaccharide_specific_immunoglobulin_isotype_responses_to_Streptococcus_pneumoniae_ L2 - http://iai.asm.org/cgi/pmidlookup?view=long&pmid=12496166 DB - PRIME DP - Unbound Medicine ER -