期刊论文详细信息
Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society
IL‐10 producing CD8+ CD122+ PD‐1+ regulatory T cells are expanded by dendritic cells silenced for Allograft Inflammatory Factor‐1
Diana M. Elizondo^11  Temesgen E. Andargie^12 
[1] Department of Biology Howard University Washington DC USA^1;Laboratório de Biologia Molecular‐Hospital Universitário Universidade Federal de Sergipe‐Aracaju Sergipe Brazil^2
关键词: cytotoxic T cells;    dendritic cells;    programmed death‐1;    suppression;    tolerogenic;    Tregs;   
DOI  :  10.1002/JLB.1A0118-010RR
学科分类:生理学
来源: Federation of American Societies for Experimental Biology
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【 摘 要 】

Allograft Inflammatory Factor‐1 (AIF1) is a cytoplasmic scaffold protein that contains Ca2+ binding EF‐hand and PDZ interaction domains important for mediating intracellular signaling complexes in immune cells. The protein plays a dominant role in both macrophage‐ and dendritic cell (DC)‐mediated inflammatory responses. This study now reports that AIF1 expression in DC is important in directing CD8+ T cell effector responses. Silencing AIF1 expression in murine CD11c+ DC suppressed antigen‐specific CD8+ T cell activation, marked by reduced CXCR3, IFNγ and Granzyme B expression, and restrained proliferation. These primed CD8+ T cells had impaired cytotoxic killing of target cells in vitro. In turn, studies identified that AIF1 silencing in DC robustly expanded IL‐10 producing CD8+ CD122+ PD‐1+ regulatory T cells that suppressed neighboring immune effector responses through both IL‐10 and PD‐1‐dependent mechanisms. In vivo studies recapitulated bystander suppression of antigen‐responsive CD4+ T cells by the CD8+ Tregs expanded from the AIF1 silenced DC. These studies further demonstrate that AIF1 expression in DC serves as a potent governor of cognate T cell responses and present a novel target for engineering tolerogenic DC‐based immunotherapies.

【 授权许可】

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