Expression of CTLA‐4 by Human Monocytes

• Published in: Scandinavian journal of immunology Vol. 55; no. 1; pp. 53 - 60
• Main Authors: Wang, X.‐B., Giscombe, R., Yan, Z., Heiden, T., Xu, D., Lefvert, A. K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science, Ltd 01-01-2002; Wiley Subscription Services, Inc
• Subjects: Abatacept; Adult; Antigens, CD; Antigens, Differentiation - chemistry; Antigens, Differentiation - genetics; Antigens, Differentiation - metabolism; Base Sequence; CD80 antigen; CD86 antigen; Cell Line; Cell Membrane - immunology; Cross-Linking Reagents; CTLA-4 Antigen; CTLA-4 protein; DNA - genetics; DNA - metabolism; g-Interferon; Gene Expression; histocompatibility antigen HLA; Humans; Immunoconjugates; In Vitro Techniques; Interferon-gamma - pharmacology; Intracellular Fluid - immunology; Medicin och hälsovetenskap; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; NF-kappa B - metabolism; Protein Kinase C - metabolism; Recombinant Proteins; Transcription Factor AP-1 - metabolism; U937 Cells
• ISSN: 0300-9475; 1365-3083
• 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)‐γ also secreted soluble CTLA‐4 in vitro. The CTLA‐4 expression was upregulated upon treatment with phorbol 12‐myristate 13‐acetate (PMA) and IFN‐γ. 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‐γ 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)‐κB 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.