Inflammation induced PD-L1-specific T cells

被引:18
作者
Munir, Shamaila [1 ]
Lundsager, Mia Thorup [1 ]
Jorgensen, Mia Aabroe [1 ]
Hansen, Morten [1 ]
Petersen, Trine Hilkjaer [2 ]
Bonefeld, Charlotte Menne [2 ]
Friese, Christina [1 ]
Met, Ozcan [1 ,2 ]
Straten, Per Thor [1 ,2 ]
Andersen, Mads Hald [1 ,2 ,3 ]
机构
[1] Copenhagen Univ Hosp, Natl Ctr Canc Immune Therapy CCIT Dk, DK-2730 Herlev, Denmark
[2] Univ Copenhagen, LEO Fdn Skin Immunol Res Ctr, Dept Immunol & Microbiol, Copenhagen, Denmark
[3] IO Biotech ApS, DK-2200 Copenhagen, Denmark
关键词
PD-L1; T-cell immunity; Inflammation; IFN-gamma; anti-Tregs; anti-regulatory T-cells; ANTIBODY; PD-L1; EXPRESSION; MOLECULES; RESPONSES; PEPTIDES; PATHWAY; SAFETY;
D O I
10.15698/cst2019.10.201
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
PD-L1-specific T cells are a natural part of the T-cell repertoire in humans. Hence, we have previously described spontaneous CD8(+) and CD4(+) T-cell reactivity against PD-L1 in the peripheral blood of patients with various cancers as well as in healthy donors. It is well described that the expression of the PD-L1 protein is introduced in cells by pro-inflammatory cytokines, e.g. IFN-gamma. In the current study, we were able to directly link inflammation with PD-L1-specific T cells by showing that inflammatory mediators such as IFN-gamma generate measurable numbers of PD-L1-specific T cells in human PBMCs as well as in in vivo models. These PD-L1-specific T cells can vigorously modulate the cell compartments of the local environment. PD-L1-specific T cells may be important for immune homeostasis by sustaining the ongoing inflammatory response by the suppression of regulatory cell function both directly and indirectly.
引用
收藏
页码:319 / 327
页数:9
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