M tuberculosis in the adjuvant modulates time of appearance of CNS-specific effector T cells in the spleen through a polymorphic site of TLR2

PLoS One. 2013;8(2):e55819. doi: 10.1371/journal.pone.0055819. Epub 2013 Feb 11.

Abstract

DC deliver information regulating trafficking of effector T cells along T-cell priming. However, the role of pathogen-derived motives in the regulation of movement of T cells has not been studied. We hereinafter report that amount of M tuberculosis in the adjuvant modulates relocation of PLP139-151 specific T cells. In the presence of a low dose of M tuberculosis in the adjuvant, T cells (detected by CDR3 BV-BJ spectratyping, the so-called "immunoscope") mostly reach the spleen by day 28 after immunization ("late relocation") in the SJL strain, whereas T cells reach the spleen by d 14 with a high dose of M tuberculosis ("early relocation"). The C57Bl/6 background confers a dominant "early relocation" phenotype to F1 (SJL×C57Bl/6) mice, allowing early relocation of T cells in the presence of low dose M tuberculosis. A single non-synonymous polymorphism of TLR2 is responsible for "early/late" relocation phenotype. Egress of T lymphocytes is regulated by TLR2 expressed on T cells. Thus, pathogens engaging TLR2 on T cells regulate directly T-cell trafficking, and polymorphisms of TLR2 condition T-cell trafficking upon a limiting concentration of ligand.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Amino Acid Sequence
  • Animals
  • Antigens / immunology
  • Base Sequence
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Central Nervous System / immunology*
  • Female
  • Genotype
  • Male
  • Mice
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / immunology*
  • Polymorphism, Single Nucleotide
  • Spleen / immunology*
  • Spleen / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Toll-Like Receptor 2 / chemistry
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*

Substances

  • Adjuvants, Immunologic
  • Antigens
  • Toll-Like Receptor 2

Grants and funding

This work was supported by: Fondazione Italiana Sclerosi Multipla (FISM) grant Nr. 28/2010/R (FR); PRIN grant from the Ministry of Education and Research (MIUR) Nr. 70103553 (FR and GD); FP7 Program, European Research Council Grant 261079 “Neurotrafficking” (GC); PRIN grant from the Ministry of Education and Research (MIUR) and Fondazione Cariverona (GC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.