Combined TLR/CD40 stimulation mediates potent cellular immunity by regulating dendritic cell expression of CD70 in vivo

J Immunol. 2007 Feb 1;178(3):1564-72. doi: 10.4049/jimmunol.178.3.1564.


We previously showed that immunization with a combination of TLR and CD40 agonists (combined TLR/CD40 agonist immunization) resulted in an expansion of Ag-specific CD8 T cells exponentially greater than the expansion observed to immunization with either agonist alone. We now show that the mechanism behind this expansion of T cells is the regulated expression of CD70 on dendritic cells. In contrast to previous results in vitro, the expression of CD70 on dendritic cells in vivo requires combined TLR/CD40 stimulation and is not significantly induced by stimulation of either pathway alone. Moreover, the exponential expansion of CD8(+) T cells following combined TLR/CD40 agonist immunization is CD70 dependent. Thus, the transition from innate stimuli (TLRs) to adaptive immunity is controlled by the regulated expression of CD70.

Publication types

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

MeSH terms

  • Animals
  • CD27 Ligand / genetics*
  • CD40 Antigens / agonists*
  • CD8-Positive T-Lymphocytes / cytology
  • Cell Proliferation
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Gene Expression Regulation / immunology
  • Immunity, Cellular*
  • Immunization
  • Mice
  • Mice, Inbred C57BL
  • Toll-Like Receptors / agonists*


  • CD27 Ligand
  • CD40 Antigens
  • Toll-Like Receptors