CiteULike: AlfonsoVicenteSuarez's O'Garra

Reversal of Tumor-induced Dendritic Cell Paralysis by CpG Immunostimulatory Oligonucleotide and Anti-Interleukin 10 Receptor Antibody

Alain Vicari — 2007-09-23T22:45:31-00:00

J. Exp. Med., Vol. 196, No. 4. (19 August 2002), pp. 541-549.

Progressing tumors in man and mouse are often infiltrated by dendritic cells (DCs). Deficient antitumor immunity could be related to a lack of tumor-associated antigen (TAA) presentation by tumor-infiltrating DCs (TIDCs) or to a functional defect of TIDCs. Here we investigated the phenotype and function of TIDCs in transplantable and transgenic mouse tumor models. Although TIDCs could encompass various known DC subsets, most had an immature phenotype. We observed that TIDCs were able to present TAA in the context of major histocompatibility complex class I but that they were refractory to stimulation with the combination of lipopolysaccharide, interferon gamma, and anti-CD40 antibody. We could revert TIDC paralysis, however, by in vitro or in vivo stimulation with the combination of a CpG immunostimulatory sequence and an anti-interleukin 10 receptor (IL-10R) antibody. CpG or anti-IL-10R alone were inactive in TIDCs, whereas CpG triggered activation in normal DCs. In particular, CpG plus anti-IL-10R enhanced the TAA-specific immune response and triggered de novo IL-12 production. Subsequently, CpG plus anti-IL-10R treatment showed robust antitumor therapeutic activity exceeding by far that of CpG alone, and elicited antitumor immune memory. 10.1084/jem.20020732

A CD4+T-cell subset inhibits antigen-specific T-cell responses and prevents colitis

Herve Groux — 2007-06-26T16:46:25-00:00

Nature, Vol. 389, No. 6652. (16 October 1997), pp. 737-742.

TH1 cells control themselves by producing interleukin-10

Anne O'Garra — 2007-05-25T19:44:10-00:00

Nature Reviews Immunology, Vol. 7, No. 6., pp. 425-428.

Identification of a Macrophage-Specific Chromatin Signature in the IL-10 Locus

Margarida Saraivaparagraph — 2007-06-15T17:46:35-00:00

J Immunol, Vol. 175, No. 2. (15 July 2005), pp. 1041-1046.

The molecular mechanisms that regulate expression of the immunosuppressive cytokine IL-10 remain poorly understood. In this study, by measuring sensitivity to DNase I digestion, we show that production of IL-10 by primary mouse bone marrow-derived macrophages stimulated through pattern recognition receptors was associated with chromatin remodeling of the IL-10 locus. We also demonstrate that the IL-10 locus is remodeled in primary Th2 cells and IL-10-producing regulatory T cells that have been differentiated in vitro. Strikingly, a novel DNase I-hypersensitive site (HSS-4.5) was identified in stimulated macrophages, but not in T cells. We show that hyperacetylated histones were recruited to this site in stimulated macrophages. Furthermore, HSS-4.5 is highly conserved and contains a putative NF-kappaB binding site. In support of a function for this site, NF-kappaB p65/RelA was recruited to HSS-4.5 in vivo and its activation was required for optimal IL-10 gene expression in LPS-stimulated macrophages.