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

被引:98
作者
Laurent, Stefania [2 ]
Carrega, Paolo [3 ]
Saverino, Daniele [4 ]
Piccioli, Patrizia
Camoriano, Marta [1 ]
Morabito, Anna [1 ]
Dozin, Beatrice [5 ]
Fontana, Vincenzo [6 ]
Simone, Rita [4 ]
Mortara, Lorenzo [7 ]
Mingari, Maria Cristina [8 ,9 ]
Ferlazzo, Guido [10 ]
Pistillo, Maria Pia [1 ]
机构
[1] Natl Inst Canc Res, Tumour Genet Unit, Breast Canc Lab, Genoa, Italy
[2] Univ Genoa, Dept Hematol & Oncol, Genoa, Italy
[3] G Gaslini Inst Children, Genoa, Italy
[4] Univ Genoa, Dept Expt Med, Genoa, Italy
[5] Natl Inst Canc Res, Clin Epidemiol Unit, Genoa, Italy
[6] Natl Inst Canc Res, Unit Epidemiol & Biostat, Genoa, Italy
[7] Univ Insubria, Sch Med, Dept Clin & Biol Sci, Varese, Italy
[8] Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy
[9] Natl Inst Canc Res, Dept Translat Oncol, Genoa, Italy
[10] Univ Messina, Sch Med, Dept Human Pathol, Messina, Italy
关键词
CTLA-4; DC; Cytokine secretion; T-cell proliferation; NF-KAPPA-B; T-CELLS; INHIBITORY RECEPTORS; TRYPTOPHAN CATABOLISM; NEGATIVE REGULATION; CYTOKINE PRODUCTION; IN-VIVO; ACTIVATION; FAMILY; LYMPHOCYTES;
D O I
10.1016/j.humimm.2010.07.007
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. (C) 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:934 / 941
页数:8
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