Direct recognition of LPS by human but not murine CD8+ T cells via TLR4 complex

Eur J Immunol. 2009 Jun;39(6):1564-72. doi: 10.1002/eji.200838866.


LPS comprises a major PAMP and is a key target of the immune system during bacterial infection. While LPS can be recognised by innate immune cells via the TLR4 complex, it is unknown whether T lymphocytes, especially CD8(+) T cells are also capable of doing so. We report here that naive human CD8(+) T cells, after activation by TCR stimulation, express surface TLR4 and CD14. These activated CD8(+) T cells can then secrete high concentrations of IFN-gamma, granzyme and perforin in response to LPS. These effects can be specifically inhibited using siRNA for TLR4. Furthermore, LPS can synergize with IL-12 to polarize the CD8(+) T cells into cytotoxic T-cell 1 (Tc1) that produce IFN-gamma but not IL-4, with or without TCR activation. Moreover, CD8(+)CD45RO(+) memory T cells constitutively expressed TLR4 and markedly enhanced IFN-gamma production when stimulated with LPS. In contrast, activated murine CD8(+) T cells lack TLR4 and CD14 expression and fail to respond to LPS for proliferation and cytokine production. Thus, human but not murine CD8(+) T cells are able to directly recognise bacterial LPS via LPS receptor complex and TLR4 provides a novel signal for the activation of effector and memory human CD8(+) T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology
  • CD3 Complex / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation / drug effects
  • Gene Expression / drug effects
  • Granzymes / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-12 / pharmacology
  • Leukocyte Common Antigens / metabolism
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / metabolism
  • Lipopolysaccharides / immunology*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Antigen 96 / genetics
  • Mice
  • Mice, Inbred C3H
  • Mice, Mutant Strains
  • Perforin / metabolism
  • RNA, Small Interfering / genetics
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / metabolism
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Antibodies
  • CD3 Complex
  • LY96 protein, human
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Lymphocyte Antigen 96
  • RNA, Small Interfering
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Perforin
  • Interleukin-12
  • Interferon-gamma
  • Leukocyte Common Antigens
  • Granzymes