Kryczek I, Wei S, Zou L et al.Cutting edge: induction of B7-H4 on APCs through IL-10: novel suppressive mode for regulatory T cells. J Immunol 177:40-44

Johns Hopkins University, Baltimore, Maryland, United States
The Journal of Immunology (Impact Factor: 4.92). 08/2006; 177(1):40-4. DOI: 10.4049/jimmunol.177.1.40
Source: PubMed


Multiple modes of suppressive mechanisms including IL-10 are thought to be implicated in CD4+CD25+ regulatory T (Treg) cell-mediated suppression. However, the cellular source, role, and molecular mechanism of IL-10 in Treg cell biology remain controversial. We now studied the interaction between Treg cells and APCs. We demonstrate that Treg cells, but not conventional T cells, trigger high levels of IL-10 production by APCs, stimulate APC B7-H4 expression, and render APCs immunosuppressive. Initial blockade of B7-H4 reduces the suppressive activity mediated by Treg cell-conditioned APCs. Further, APC-derived, rather than Treg cell-derived, IL-10 is responsible for APC B7-H4 induction. Therefore, Treg cells convey suppressive activity to APCs by stimulating B7-H4 expression through IL-10. Altogether, our data provide a novel cellular and molecular mechanism for Treg cell-mediated immunosuppression at the level of APCs, and suggest a plausible mechanism for the suppressive effect of IL-10 in Treg cell-mediated suppression.

Download full-text


Available from: Huanbin Xu, Aug 13, 2015
  • Source
    • "Interleukin 10 (IL-10) and transforming growth factor b (TGFb ) are anti-inflammatory and immunosuppressive cytokines that can contribute to the immune escape of neoplastic cells (Kryczek et al., 2006; Matsuda et al., 1994; Thomas & Massague, 2005). IL- 10 prevents antigen presentation by macrophages and dendritic cells, reducing the expression of the MHC class I molecules on the cell surface (Matsuda et al., 1994), regulating the differentiation of T regulatory (T reg) cells (Kryczek et al., 2006) and inducing the formation of a tumour cell phenotype resistant to the action of cytotoxic T lymphocytes (CTLs) (Kurte et al., 2004). TGF-b contributes to the loss of differentiation of tumour cells (Ma et al., 2013), angiogenesis (Pertovaara et al., 1994) and the synthesis of proteolytic enzymes (Kim, Shang, Chen, Pflugfelder, & Li, 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The aim of this study was to evaluate the expression of IL-10 and TGF-β2 in oral squamous cell carcinoma (OSCC) and its relationship with prognostic clinical and microscopic parameters. Design: Immunohistochemistry was used to assess the expression of IL-10 and TGF-β2 in OSCC samples from 43 patients who had undergone surgical excision and neck dissection. Metastatic lymph nodes were included in the study (n=23). Samples of healthy oral mucosa (n=20) were used as controls. The sections were evaluated using a semi-quantitative method in conjunction with staining intensity. Results: Our findings showed that the expression of IL-10 and TGF-β2 by neoplastic and stromal cells was high in most of the OSCC samples (>70% of samples), especially when compared to the controls (≅10% of samples) (P<0.05). OSCC neoplastic cells in cervical lymph nodes were also positive for IL-10 and TGF-β2. An association between high expression of IL-10 by neoplastic cells and advanced clinical stage (T3-T4) was verified (P=0.02). Although not statistically significant, the expression of TGF-β2 was also augmented in advanced stage tumours. Conclusions: These data suggest that the ability of OSCC neoplastic cells to secrete immunosuppressive cytokines could contribute to clinical progression by maintaining a microenvironment conducive to evasion and tumour proliferation.
    Full-text · Article · Oct 2015 · Archives of oral biology
  • Source
    • "Furthermore, Tregs may convert APCs to become themselves immunosuppressive (78). It has also been proposed that Tregs act by competing with other cells for growth factors, particularly IL-2 (79, 80). "
    [Show abstract] [Hide abstract]
    ABSTRACT: To maintain immunological balance the organism has to be tolerant to self while remaining competent to mount an effective immune response against third-party antigens. An important mechanism of this immune regulation involves the action of regulatory T-cell (Tregs). In this mini-review, we discuss some of the known and proposed mechanisms by which Tregs exert their influence in the context of immune regulation, and the contribution of mathematical modeling for these mechanistic studies. These models explore the mechanisms of action of regulatory T cells, and include hypotheses of multiple signals, delivered through simultaneous antigen-presenting cell (APC) conjugation; interaction of feedback loops between APC, Tregs, and effector cells; or production of specific cytokines that act on effector cells. As the field matures, and competing models are winnowed out, it is likely that we will be able to quantify how tolerance-inducing strategies, such as CD4-blockade, affect T-cell dynamics and what mechanisms explain the observed behavior of T-cell based tolerance.
    Full-text · Article · Nov 2013 · Frontiers in Immunology
  • Source
    • "Recently, T reg cells have also been shown to trigger high levels of IL-10 production by APCs and in turn stimulate B7-H4 expression in an autocrine fashion and render these APCs immunosuppressive (Kryczek et al., 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Peripheral immune tolerance requires a controlled balance between the maintenance of self-tolerance and the capacity to engage protective immune responses against pathogens. Dendritic cells (DCs) serve as sentinels of the immune system by sensing environmental and inflammatory signals, and play an essential role in the maintenance of immune tolerance. To achieve this, DC play a key role in dictating the outcome of immune responses by influencing the balance between inflammatory or Foxp3(+) regulatory T (T(reg)) cell responses. At the heart of this immunological balance is a finely regulated DC and T(reg) cell crosstalk whereby T(reg) cells modulate DC phenotype and function, and DC drive the differentiation of Foxp3(+) T(reg) cells in order to control immune responses. This review will focus on recent advances, which highlight the importance of this bidirectional DC and T(reg) cell crosstalk during the induction of tolerance and organ-specific autoimmunity. More specifically, we will discuss how T(reg) cells modulate DC function for the suppression of inflammatory responses and how DC subsets employ diverse mechanisms to drive differentiation of T(reg) cells. Finally, we will discuss the therapeutic potential of tolerogenic DCs for the induction of tolerance in autoimmune diseases.
    Full-text · Article · Jun 2012 · Frontiers in Immunology
Show more