4-1BB costimulation promotes human T cell adhesion to fibronectin

Cell Immunol. 1999 Feb 25;192(1):13-23. doi: 10.1006/cimm.1998.1435.


CD28 and 4-1BB (CD137) are costimulatory molecules for T cells. In this study we investigated the role of 4-1BB in T cell adhesion to fibronectin (FN). Unlike CD28, 4-1BB is present in only a small subset of T cells prepared from fresh human peripheral blood mononuclear cells, but was induced after prolonged TCR/CD28 activation in vitro. 4-1BB-expressing T cells were characteristically unique in their strong responsiveness to FN. Anti-4-1BB cross-linking synergized CD28 costimulation by lowering the threshold of CD3 signal required for CD28-mediated maximal proliferative response. In addition to increasing proliferative responses, 4-1BB promoted T cell adhesion to FN in the presence of CD28 costimulation. 4-1BB-mediated cell adhesion to FN was blocked by anti-beta1 integrin, suggesting that 4-1BB mediates beta1 integrin activation. The role of 4-1BB in inducing CD4(+) T cell adhesion to FN was confirmed by showing that the human leukemic CD4(+) T cell line, Jurkat, when transfected with cDNA encoding 4-1BB, became adherent to FN with anti-4-1BB stimulation. Taken together, our results suggest that 4-1BB-promoted T cell adhesion to extracellular matrix proteins is an important postactivation process for T cell migration.

Publication types

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

MeSH terms

  • Antigens, CD
  • CD28 Antigens / metabolism
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / physiology*
  • Cell Adhesion*
  • Drug Synergism
  • Fibronectins / metabolism*
  • Humans
  • Integrin beta1 / metabolism
  • Jurkat Cells
  • Lymphocyte Activation
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / physiology*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / physiology*
  • Signal Transduction
  • Tumor Necrosis Factor Receptor Superfamily, Member 9


  • Antigens, CD
  • CD28 Antigens
  • CD3 Complex
  • Fibronectins
  • Integrin beta1
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TNFRSF9 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 9