Human decidual stromal cells suppress cytokine secretion by allogenic CD4+ T cells via PD-1 ligand interactions  

Oleh:

Nagamatsu, Takeshi ; Schust, Danny J. ; Sugimoto, Jun ; Barrier, Breton F.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Human Reproduction vol. 24 no. 12 (Dec. 2009), page 3160-3171 .
Topik: cell culture; cell signaling; immunology

Ketersediaan

Perpustakaan FK Nomor Panggil: H07.K.2009.04 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

BACKGROUND Although previous reports suggest an antigen-presenting function for decidual stromal cells (DSCs), the relevance of cell-to-cell communication between DSCs and T cells at the human feto-maternal interface has not been fully elucidated. Therefore, we investigated the presence and function of human DSC-expressed B7-H1 and B7-DC co-stimulatory ligands. B7-H1 and B7-DC on peripheral antigen-presenting cells (APC) typically inhibit T cell activation after binding to their corresponding receptor, programmed death-1 (PD-1). METHODS DSCs were isolated from human term decidua. The expression of B7-H1/B7-DC and HLA-DR and their alteration following IFN-? and/or TNF-a stimulation were assessed. DSCs with or without IFN-? pretreatment were co-cultured with allogenic CD4+ T cells. The effect of PD-1:B7-H1/B7-DC and T cell receptor (TCR):HLA-DR interactions on T cell cytokine production was evaluated by adding blocking antibodies. RESULTS DSCs constitutively expressed B7-H1 and B7-DC, as well as small amounts of HLA-DR. Exogenous IFN-? and TNF-a up-regulated the B7-H1/-DC expression on DSCs, whereas HLA-DR expression was increased only by IFN-?. IFN-? pretreatment of DSCs stimulated T cell cytokine production through HLA-DR up-regulation. B7-H1 blockade on DSCs strongly enhanced T cell cytokine production (IFN-?, TNF-a and IL-2), whereas B7-DC blockade had similar but more modest effects. Blockade of both B7-H1 and B7-DC resulted in additive effects. CONCLUSIONS Our findings support the categorization of human DSCs as non-professional APCs and suggest that PD-1 ligands on DSCs, together with major histocompatibility complex class II, may play a crucial role in the regulation of decidual CD4+ T cell cytokine production. This helps to maintain a balanced cytokine milieu at the feto-maternal interface.

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