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This information is current as Cells T + Regulatory Properties in Memory CD 4 Induce Antigen-Specific Anergy and Different Immunosuppressive Cytokines Tolerogenic Dendritic Cells Generated with
| Content Provider | Semantic Scholar |
|---|---|
| Author | Torres-Aguilar, Honorio Aguilar-Ruiz, Sergio R. González-Pérez, Gabriela Munguı́a, Rosario Bajaña, Sandra Meraz-Ríos, Marco Antonio Sanchez-Torres, Carmen |
| Copyright Year | 2010 |
| Abstract | Dendritic cells (DCs) are professional APCs involved in the initiation of both immunity and immunological tolerance. In autoim-mune diseases or graft rejections, most reactive lymphocytes are effector/memory cells. It is believed that memory T cells are more resistant to tolerance induction than naive lymphocytes; however, studies on mechanisms for their efficient tolerization are still scarce. In this study, we generated human monocyte-derived DCs by culture with GM-CSF and IL-4 (control DCs), as well as tolerogenic DCs (tDCs) by adding IL-10, IL-10/TGF-b1, or IL-10/IL-6. Cells were maturated with TNF-a/PGE 2. Compared with control DCs, tDCs had similar expression of HLA-DR, CD80, and CD86, lower expression of CD40, higher levels of macrophage markers, enhanced endocytic ability, increased secretion of IL-6, IL-10 (only tDCs generated with IL-10 and tDCs generated with IL-10/IL-6), and PGE 2 , and lower secretion of IL-12 and IL-23. In vitro, tDCs had the capacity to induce anergy in tetanus toxoid-specific memory CD4 + T cells, whereas the proliferative response to an unrelated Ag was intact. Anergy could be reverted upon exposure to IL-2. tDC-primed T cells have low suppressive ability. Nevertheless, the generation of both anergic and regulatory T cells was more efficient with tDCs generated with IL-10/TGF-b1. Microarray-based gene expression profiling reflected modulated expression of several transcripts in tDCs. Surface CLIP–HLA-DR complexes and intracellular thrombospondin-1 were increased in the three tDCs. CD39 was highly expressed only in tDC-TGF, which correlated with increased adenosine production. We propose that these molecules, together with IL-10 and prostanoids, are key factors to induce Ag-specific tolerance in memory T cells. D endritic cells (DCs) include a heterogeneous family of professional APCs involved in the initiation of both immunity and immunological tolerance (1). T cell peripheral tolerance can be generated and maintained by DCs, leading to the promotion of anergy, immune deviation, deletion of self-reactive lymphocytes, or generation of regulatory T cells (Tregs) (2). Tolerogenic DCs (tDCs) are characterized by low constitutive expression of positive costimulatory molecules compared with inhibitory factors (i.e., Ig-like transcripts [ILT] 2, 3, 4, B7-H1), as well as by their ability to suppress a broad range of effector T cell responses (3). Immature DCs (iDCs) and semi-mature developmental stages of DC differentiation and some subtypes of DCs, such as resting plasmacytoid DC, are prone to induce T cell anergy and Treg development (4–8). Moreover, alternatively activated mature DCs exposed to various suppressive agents, as well as to immunomodulatory drugs, … |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/184/4/1765.full.pdf |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/early/2010/01/18/jimmunol.0902133.full.pdf |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/184/4/1765.full.pdf?with-ds=yes |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
