Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
11019363 | International Immunopharmacology | 2018 | 7 Pages |
Abstract
Naïve CD4 T cells can be converted to double-negative regulatory T cells (DNT) by mature dendritic cells (mDCs) and IL-2 stimulation, with IL-2 enhancing the proliferation and Perforin expression of DNT. However, the molecules that affect the conversion of DNT are still not clear. Here, we investigated the effects of Ox40 on the conversion and function of DNT in vitro and in vivo without IL-2. We found that OX86 (an Ox40 agonist) increased the conversion rate of DNT but failed to enhance the suppressive function of DNT. Ox40 deficiency profoundly decreased the conversion rate and suppressive function of DNT. This suppression decline was caused by effects of Ox40 on proliferation and apoptosis independent of Perforin, Granzyme B and Fas ligand. Ox40 deficiency influenced the regulatory function of DNT through multiple signals, such as Cxcr3, Cd160 and Cd30, independently of Prf, Gzmb and Fasl. In conclusion, we elucidated that Ox40 promotes the conversion and maintenance of DNT. Ox40 deficiency reduced the regulatory function of DNT both in vitro and in vivo by regulating proliferation, apoptosis, and suppression-related genes.
Keywords
Granzyme BTregsCD30FACSmDCsBcl-xLGM-CSFIL-2CXCR3DNTBcl-2OX40T effector cellsCD160FASmRNA sequencingRNA-seqMLRMFIPRFqPCRGZMBinterleukin 2Teffsfluorescence-activated cell sortingDouble negative T cellsreal-time quantitative PCRmature dendritic cellsRegulatory T cellsmedian fluorescence intensityGranulocyte macrophage colony stimulating factorFas LigandFasLB cell lymphoma 2B-cell lymphoma-extra largecomplete culture mediumknockoutwild typeGene ontologymixed lymphocyte reactionPerforin
Related Topics
Life Sciences
Immunology and Microbiology
Immunology
Authors
Kai Liu, Huichu Ye, Jin Zhou, Yue Tian, Hufeng Xu, Xuelian Sun, Dong Zhang,