Comparison of OX40 ligand and CD70 in the promotion of CD4+ T cell responses

J Immunol. 2010 Aug 15;185(4):2106-15. doi: 10.4049/jimmunol.1000172. Epub 2010 Jul 16.


The TNF superfamily members CD70 and OX40 ligand (OX40L) were reported to be important for CD4(+) T cell expansion and differentiation. However, the relative contribution of these costimulatory signals in driving CD4(+) T cell responses has not been addressed. In this study, we found that OX40L is a more important determinant than CD70 of the primary CD4(+) T cell response to multiple immunization regimens. Despite the ability of a combined TLR and CD40 agonist (TLR/CD40) stimulus to provoke appreciable expression of CD70 and OX40L on CD8(+) dendritic cells, resulting CD4(+) T cell responses were substantially reduced by Ab blockade of OX40L and, to a lesser degree, CD70. In contrast, the CD8(+) T cell responses to combined TLR/CD40 immunization were exclusively dependent on CD70. These requirements for CD4(+) and CD8(+) T cell activation were not limited to the use of combined TLR/CD40 immunization, because vaccinia virus challenge elicited primarily OX40L-dependent CD4 responses and exclusively CD70-dependent CD8(+) T cell responses. Attenuation of CD4(+) T cell priming induced by OX40L blockade was independent of signaling through the IL-12R, but it was reduced further by coblockade of CD70. Thus, costimulation by CD70 or OX40L seems to be necessary for primary CD4(+) T cell responses to multiple forms of immunization, and each may make independent contributions to CD4(+) T cell priming.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • CD27 Ligand / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD40 Antigens / genetics
  • CD40 Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Female
  • Flow Cytometry
  • Immunization / methods
  • Listeria monocytogenes / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • OX40 Ligand / immunology*
  • Signal Transduction / immunology
  • Toll-Like Receptors / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Vaccinia virus / immunology


  • CD27 Ligand
  • CD40 Antigens
  • OX40 Ligand
  • Toll-Like Receptors
  • Tumor Necrosis Factor Receptor Superfamily, Member 7