Lipopolysaccharide potentiates effector T cell accumulation into nonlymphoid tissues through TRIF

J Immunol. 2009 May 1;182(9):5322-30. doi: 10.4049/jimmunol.0803616.


LPS is a natural adjuvant that potentiates Ag-specific T cell survival and Th1 differentiation by stimulating MyD88 and Toll/IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) signaling pathways. In this study, we reveal the TRIF pathway is critical for amplifying murine effector T cell accumulation into nonlymphoid tissues following immunization with Ag plus LPS. Although LPS increased the accumulation of splenic T cells in TRIF-deficient mice, markedly fewer T cells were recovered from liver and lung in comparison to wild type. Most of the T cells primed in TRIF-deficient mice failed to up-regulate CXCR3 and had an overall reduced capacity to produce IFN-gamma, demonstrating effector T cell differentiation was linked to their migration. To investigate the role of TRIF-dependent cytokines, neutralization studies were performed in wild type mice. Although TNF neutralization reduced T cell numbers, its coneutralization with IL-10 unexpectedly restored the T cells, suggesting the balance between pro- and anti-inflammatory cytokines influences T cell survival rather than their magnitude. To investigate a role for costimulatory molecules, we tested whether the T cell defect in TRIF-deficient mice could be corrected with enforced costimulation. Boosting with a CD40 agonist in addition to LPS restored the effector CD8 T cell response in livers of TRIF-deficient mice while only partially restoring CD4 T cells, suggesting that LPS primes CD8 and CD4 T cell immunity through different mechanisms. Overall, our data support targeting TRIF for vaccines aimed to direct immune responses to nonlymphoid tissues.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Vesicular Transport / deficiency
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / physiology*
  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / transplantation
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cell Movement / immunology*
  • Cells, Cultured
  • Lipopolysaccharides / administration & dosage*
  • Liver / cytology
  • Liver / immunology*
  • Lung / cytology
  • Lung / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Signal Transduction / immunology


  • Adaptor Proteins, Vesicular Transport
  • Adjuvants, Immunologic
  • Lipopolysaccharides
  • TICAM-1 protein, mouse