Requirements for the functional expression of OX40 ligand on human activated CD4+ and CD8+ T cells

Hum Immunol. 2007 Jul;68(7):563-71. doi: 10.1016/j.humimm.2007.03.012. Epub 2007 Apr 13.


Interaction between OX40 expressed on activated T cells and its ligand (OX40L) on antigen presenting cells (APC) provides a co-stimulatory signal for T cells to promote acquired immunity. In the present study, we have examined various culture conditions for optimum OX40L expression on T cells stimulated with immobilized anti-CD3/CD28 monoclonal antibodies (mAbs). Although the day 3 primed T cells expressed minimal OX40L, after repeated stimulations both the CD4+ and CD8+ T cells became OX40L positive as determined by flow cytometry. Interleukin (IL)-12 interfered with the OX40L expression. Among activated T cells, a higher frequency of CD8+ T cells expressed OX40L than CD4+ T cells. By blocking OX40L-OX40 interaction by an anti-OX40 mAb, the number of OX40L+ T cells significantly increased. Screening of various cytokines showed that transforming growth factor (TGF)-beta1 was capable of induction of OX40L on the activated T cells within 3 days. The OX40L expressed on T cells was functional, as they bound soluble OX40 and stimulated human immunodeficiency virus-1 (HIV-1) production from cell lines chronically infected with HIV-1 and expressing OX40. Altogether the present study findings indicate that functional OX40L is inducible on human activated CD4+ and CD8+ T cells, and that the expression is enhanced by TGF-beta1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • CD28 Antigens / immunology
  • CD28 Antigens / metabolism
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Culture Techniques
  • Cytokines / immunology
  • Cytokines / metabolism
  • Flow Cytometry
  • HIV-1 / metabolism
  • Humans
  • Lymphocyte Activation
  • OX40 Ligand / biosynthesis
  • OX40 Ligand / immunology
  • OX40 Ligand / metabolism*
  • Receptors, OX40 / immunology
  • Receptors, OX40 / metabolism*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Transforming Growth Factor beta1 / immunology
  • Transforming Growth Factor beta1 / metabolism*


  • Antibodies, Monoclonal
  • CD28 Antigens
  • CD3 Complex
  • Cytokines
  • OX40 Ligand
  • Receptors, OX40
  • Recombinant Proteins
  • Transforming Growth Factor beta1