TLR2 engagement on memory CD8(+) T cells improves their cytokine-mediated proliferation and IFN-gamma secretion in the absence of Ag

Eur J Immunol. 2009 Oct;39(10):2673-81. doi: 10.1002/eji.200939627.


Persistence of memory CD8(+) T cells is known to be largely controlled by common gamma chain cytokines, such as IL-2, IL-7 and IL-15. However, other molecules may be involved in this phenomenon. We show here that TLR2(-/-) mice have a decreased frequency of memory phenotype CD8(+) T cells when compared with WT mice. This prompted us to investigate the role of TLR2 in the homeostasis of memory CD8(+) T cells. We describe here a new TLR2-dependent mechanism which, in the absence of specific antigen, directly controls memory CD8(+) T-cell proliferation and IFN-gamma secretion. We demonstrate that TLR2 engagement on memory CD8(+) T cells increases their proliferation and expansion induced by IL-7 both in vitro and in vivo. We also show that TLR2 ligands act in synergy with IL-2 to induce IFN-gamma secretion in vitro. Both conclusions are obtained with spontaneously arising memory phenotype and antigen-specific memory CD8(+) T cells. Altogether, our data support the idea that continuous TLR2 signaling in response to microbial stimuli or endogenous danger signals might directly contribute to the maintenance of the diversity memory CD8(+) T cells in the organism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens / immunology*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / transplantation
  • Cell Count
  • Cell Proliferation / drug effects*
  • Cytokines / pharmacology*
  • Immunologic Memory / immunology*
  • Interferon-gamma / metabolism*
  • Interleukin-12 / pharmacology
  • Interleukin-15 / pharmacology
  • Interleukin-18 / pharmacology
  • Interleukin-2 / pharmacology
  • Interleukin-7 / pharmacology
  • Lipopeptides / pharmacology
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / transplantation
  • Toll-Like Receptor 2 / agonists
  • Toll-Like Receptor 2 / physiology*


  • Antigens
  • Cytokines
  • Interleukin-15
  • Interleukin-18
  • Interleukin-2
  • Interleukin-7
  • Lipopeptides
  • Pam(3)CSK(4) peptide
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Interleukin-12
  • Interferon-gamma