Expression and function of 4-1BB during CD4 versus CD8 T cell responses in vivo

Eur J Immunol. 2004 Mar;34(3):743-751. doi: 10.1002/eji.200324278.


4-1BBL(-/-) mice have a defect in recall CD8+ T cell responses to viruses, whereas CD4+ T cell responses to virus are unimpaired in these mice. In contrast, both CD4+ and CD8+ T cells respond to 4-1BB ligand (4-1BBL) in vitro. To clarify the role of 4-1BB/4-1BBL in CD4+ versus CD8+ T cell responses in vivo, we compared CD4 (OT-II) and CD8 (OT-I) TCR transgenic T cells responding to the same antigen in an in vivo adoptive transfer model in 4-1BBL(+/+) versus 4-1BBL(-/-) mice. During primary and secondary responses, expression of 4-1BB on in vivo-activated TCR transgenic T cells was earlier and more transient than previously observed in vitro, correlating with expression of the early activation antigen CD69 and preceding the transition to the CD44hi state. Although 4-1BB is expressed early in the primary response, there was no effect of 4-1BBL deficiency on initial CD8 T cell expansion and only a minor effect on initial CD4 T cell expansion. The major effect of 4-1BB/4-1BBL interaction is on the T cell recall response. This is due to effects of 4-1BBL on maintenance of T cell numbers at the end of the primary response with additional effects of 4-1BBL on secondary expansion of T cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-1BB Ligand
  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / transplantation
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / transplantation
  • Genes, T-Cell Receptor
  • Immunologic Memory
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / physiology*


  • 4-1BB Ligand
  • Tnfsf9 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Ovalbumin