A reduced antigen load in vivo, rather than weak inflammation, causes a substantial delay in CD8+ T cell priming against Mycobacterium bovis (bacillus Calmette-Guerin): J.Immunol.

Download
  1. Get@NRC: A reduced antigen load in vivo, rather than weak inflammation, causes a substantial delay in CD8+ T cell priming against Mycobacterium bovis (bacillus Calmette-Guerin): J.Immunol. (Opens in a new window)
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titleJ Immunol
Volume179
Issue1
Pages211220; # of pages: 10
Subjectadministration & dosage; Animals; antagonists & inhibitors; ANTIGEN; Antigen Presentation; Antigens; Antigens,Bacterial; Bacillus; Bacteria; BCG Vaccine; Canada; CD8-Positive T-Lymphocytes; cell; CELLS; Cytotoxicity,Immunologic; Dose-Response Relationship,Immunologic; Female; G0 Phase; Immunologic Memory; immunology; INFECTION; Inflammation; Inflammation Mediators; Lymphocyte Activation; MECHANISMS; metabolism; Mice; Mice,Inbred C57BL; Mice,Transgenic; Microbiology; MOLECULAR; Mycobacterium; Mycobacterium bovis; Ovalbumin; physiology; Time Factors
AbstractRegardless of the dose of Ag, Ag presentation occurs rapidly within the first few days which results in rapid expansion of the CD8+ T cell response that peaks at day 7. However, we have previously shown that this rapid priming of CD8+ T cells is absent during infection of mice with Mycobacterium bovis (bacillus Calmette-Guerin (BCG)). In this study, we have evaluated the mechanisms responsible for the delayed CD8+ T cell priming. Because BCG replicates poorly and survives within phagosomes we considered whether 1) generation of reduced amounts of Ag or 2) weaker activation by pathogen-associated molecular patterns (PAMPs) during BCG infection is responsible for the delay in CD8+ T cell priming. Using rOVA-expressing bacteria, our results indicate that infection of mice with BCG-OVA generates greatly reduced levels of OVA, which are 70-fold lower in comparison to the levels generated during infection of mice with Listeria monocytogenes-expressing OVA. Furthermore, increasing the dose of OVA, but not PAMP signaling during BCG-OVA infection resulted in rapid Ag presentation and consequent expansion of the CD8+ T cell response, indicating that the generation of reduced Ag levels, not lack of PAMP-associated inflammation, was responsible for delayed priming of CD8+ T cells. There was a strong correlation between the relative timing of Ag presentation and the increase in the level of OVA in vivo. Taken together, these results reveal that some slowly replicating pathogens, such as mycobacteria, may facilitate their chronicity by generating reduced Ag levels which causes a substantial delay in the development of acquired immune responses
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberRUSSELL2007
NPARC number9365489
Export citationExport as RIS
Report a correctionReport a correction
Record identifierae0ea2cf-a662-467d-9e71-35b3ec81e1e3
Record created2009-07-10
Record modified2016-05-09
Bookmark and share
  • Share this page with Facebook (Opens in a new window)
  • Share this page with Twitter (Opens in a new window)
  • Share this page with Google+ (Opens in a new window)
  • Share this page with Delicious (Opens in a new window)