Expression of CTLA-4 by human monocytes

Scand J Immunol. 2002 Jan;55(1):53-60. doi: 10.1046/j.0300-9475.2001.01019.x.


Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is a receptor present on T cells that plays a critical role in the downregulation of antigen-activated immune responses. CTLA-4 interacts with the ligands CD80 and CD86 on antigen-presenting cells (APC), and also directs the assembly of inhibitory signalling complexes that lead to quiescence or anergy. In this study, we show that human monocytes constitutively express CTLA-4. About 3% of monocytes expressed CTLA-4 on the cell surface, whereas the intracellular expression was higher and present in about 20% of the monocytes. The sequences of the cDNAs from human monocytes were identical to the sequences of CTLA-4 from T cells. Expression of CTLA-4 was also confirmed in the activated myelomonocytic cell lines U937 and THP-1. Monocytes, but not T cells, activated by interferon (IFN)-gamma also secreted soluble CTLA-4 in vitro. The CTLA-4 expression was upregulated upon treatment with phorbol 12-myristate 13-acetate (PMA) and IFN-gamma. This increased expression could be partially abolished by staurosporine, an inhibitor of protein kinase C (PKC). Ligation of CTLA-4 in the monocyte-like cell-line U937 with antibodies against CTLA-4 partially inhibited the proliferation of cells and the upregulation of cell-surface markers CD86, CD54, HLA-DR and HLA-DQ induced by IFN-gamma and Staphylococcus aureus, Cowan I strain (SAC). Ligation of CTLA-4 suppressed the PMA-stimulated activation of transcription activator protein 1 (AP-1) and nuclear factor (NF)-kappaB in the U937 cell line, indicating the involvement of an inhibitory signal transduction. These data provide the first evidence that CTLA-4 is constitutively expressed by monocytes and thus might be important for the regulation of immune mechanisms associated with monocytes.

MeSH terms

  • Abatacept
  • Adult
  • Antigens, CD
  • Antigens, Differentiation / chemistry
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism*
  • Base Sequence
  • CTLA-4 Antigen
  • Cell Line
  • Cell Membrane / immunology
  • Cross-Linking Reagents
  • DNA / genetics
  • DNA / metabolism
  • Gene Expression
  • Humans
  • Immunoconjugates*
  • In Vitro Techniques
  • Interferon-gamma / pharmacology
  • Intracellular Fluid / immunology
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Monocytes / metabolism
  • NF-kappa B / metabolism
  • Protein Kinase C / metabolism
  • Recombinant Proteins
  • Transcription Factor AP-1 / metabolism
  • U937 Cells


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cross-Linking Reagents
  • Immunoconjugates
  • NF-kappa B
  • Recombinant Proteins
  • Transcription Factor AP-1
  • Abatacept
  • Interferon-gamma
  • DNA
  • Protein Kinase C