4-1BB (CD137) controls the clonal expansion and survival of CD8 T cells in vivo but does not contribute to the development of cytotoxicity

Eur J Immunol. 2002 Feb;32(2):521-9. doi: 10.1002/1521-4141(200202)32:2<521::AID-IMMU521>3.0.CO;2-X.


4-1BB is expressed on activated T cells. We analyzed the role of 4-1BB during the CD8 T cell response of OT-I TCR-transgenic T cells to ovalbumin. In vitro, blocking 4-1BB during peptide presentation reduced proliferation of naive CD8 T cells, but did not affect the generation of CTL. Using an in vivo adoptive transfer model, clonal expansion of CD8 T cells to whole protein in adjuvant was significantly reduced when 4-1BB was blocked, with 50-70% fewer CD8 T cells accumulating. This was due to a reduction in T cell division and to enhanced apoptosis of CD8 T cells that had undergone many divisions. T cells generated in the absence of 4-1BB were impaired in their ability to secrete IFN-gamma whereas CTL activity of the T cells that survived was unaffected. These findings demonstrate that 4-1BB contributes to clonal expansion, survival, and development of Tc1 cells when protein antigen is encountered by primary CD8 T cells in an inflammatory environment in vivo.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen Presentation
  • Antigens, CD
  • Apoptosis
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Division
  • Cell Survival
  • Cytotoxicity, Immunologic
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Nerve Growth Factor / metabolism*
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Signal Transduction
  • Tumor Necrosis Factor Receptor Superfamily, Member 9


  • Antigens, CD
  • Receptors, Antigen, T-Cell
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf9 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Ovalbumin