4.6 Article

M tuberculosis in the Adjuvant Modulates Time of Appearance of CNS-Specific Effector T Cells in the Spleen through a Polymorphic Site of TLR2

Journal

PLOS ONE
Volume 8, Issue 2, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0055819

Keywords

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Funding

  1. Fondazione Italiana Sclerosi Multipla (FISM) [28/2010/R]
  2. PRIN from the Ministry of Education and Research (MIUR) [70103553]
  3. European Research Council [261079]
  4. Fondazione Cariverona
  5. European Research Council (ERC) [261079] Funding Source: European Research Council (ERC)

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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 (SJLxC57Bl/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.

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