CTLA-4 is expressed by human monocyte-derived dendritic cells and regulates their functions

Stefania Laurent, Paolo Carrega, Daniele Saverino, Patrizia Piccioli, Marta Camoriano, Anna Morabito, Beatrice Dozin, Vincenzo Fontana, Rita Simone, Lorenzo Mortara, Maria Cristina Mingari, Guido Ferlazzo, Maria Pia Pistillo

Research output: Contribution to journalArticlepeer-review

Abstract

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is the major negative regulator of T-cell responses, although growing evidence supports its wider role as an immune attenuator that may also act in other cell lineages. Here, we have analyzed the expression of CTLA-4 in human monocytes and monocyte-derived dendritic cells (DCs), and the effect of its engagement on cytokine production and T-cell stimulatory activity by mature DCs. CTLA-4 was highly expressed on freshly isolated monocytes, then down-modulated upon differentiation toward immature DCs (iDCs) and it was markedly upregulated on mature DCs obtained with different stimulations (lipopolysaccharides [LPS], Poly:IC, cytokines). In line with the functional role of CTLA-4 in T cells, treatment of mDCs with an agonistic anti-CTLA-4 mAb significantly enhanced secretion of regulatory interleukin (IL)-10 but reduced secretion of IL-8/IL-12 pro-inflammatory cytokines, as well as autologous CD4+ T-cell proliferation in response to stimulation with recall antigen purified protein derivative (PPD) loaded-DCs. Neutralization of IL-10 with an anti-IL-10 antibody during the mDCs-CD4+ T-cell co-culture partially restored the ability of anti-CTLA-4-treated mDCs to stimulate T-cell proliferation in response to PPD. Taken together, our data provide the first evidence that CTLA-4 receptor is expressed by human monocyte-derived mDCs upon their full activation and that it exerts immune modulatory effects.

Original languageEnglish
Pages (from-to)934-941
Number of pages8
JournalHuman Immunology
Volume71
Issue number10
DOIs
Publication statusPublished - Oct 2010

Keywords

  • CTLA-4
  • Cytokine secretion
  • DC
  • T-cell proliferation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Fingerprint Dive into the research topics of 'CTLA-4 is expressed by human monocyte-derived dendritic cells and regulates their functions'. Together they form a unique fingerprint.

Cite this