Inhibition of antibody production in vivo by pre-stimulation of Toll-like receptor 4 before antigen priming is caused by defective B-cell priming and not impairment in antigen presentation

Inhibition of antibody production in vivo by pre-stimulation of Toll-like receptor 4 before antigen priming is caused by defective B-cell priming and not impairment in antigen presentation

Stimulation of Toll-like receptor 4 (TLR4) induces not only innate but also adaptive immune responses, and has been suggested to exert adjuvant effects. Additional to such positive effects, pre-stimulation of TLR4 induces endotoxin tolerance where animals are unresponsive to subsequent lethal challe...

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Bibliographic Details
Published in:International immunology Vol. 25; no. 2; pp. 117 - 128
Main Authors: Rachmawati, Nurlaely Mida, Fukudome, Kenji, Tsuneyoshi, Naoko, Bahrun, Uleng, Tsukamoto, Hiroki, Yanagibashi, Tsutomu, Nagai, Yoshinori, Takatsu, Kiyoshi, Ohta, Shoichiro, Kimoto, Masao
Format: Journal Article
Language:English
Published: England 01-02-2013
Subjects:
Adjuvants, Immunologic
Animals
Antibodies, Monoclonal - immunology
Antibody Formation - immunology
Antibody Specificity
Antigen Presentation - immunology
Antigen-Antibody Reactions
Antigens - immunology
B-Lymphocytes - immunology
Cross-Priming - immunology
Female
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Toll-Like Receptor 4 - agonists
Toll-Like Receptor 4 - immunology
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Summary:Stimulation of Toll-like receptor 4 (TLR4) induces not only innate but also adaptive immune responses, and has been suggested to exert adjuvant effects. Additional to such positive effects, pre-stimulation of TLR4 induces endotoxin tolerance where animals are unresponsive to subsequent lethal challenges with lipopolysaccharide (LPS). We examined the effects of pre-stimulation of TLR4 using an agonistic anti-TLR4 mAb (UT12) on antibody production in vivo. Pre-injection of UT12 prior to both primary and secondary immunization completely inhibited antigen-specific antibody responses. Cellular analysis revealed that the inhibition was not due to impairment of T-cell activation. Accordingly, T-helper activities in UT12 pre-injected mice were not impaired. In contrast, B-cell priming was defective in UT12 pre-injected mice. The observation that the expression of activation markers such as CD69 and CD86 on B cells was blocked by UT12 pre-injection supports this. Interestingly, UT12 pre-injection only showed inhibitory effects at the primary and not the secondary immunization. These results provide important information concerning the regulatory mechanisms of antibody production, especially in endotoxin-tolerant states.
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ISSN:0953-8178
1460-2377
DOI:10.1093/intimm/dxs096