ABSTRACT
Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4+ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4+ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Subject(s)
Animals , Humans , Mice , CD4-Positive T-Lymphocytes/pathology , Cell Differentiation , Encephalomyelitis, Autoimmune, Experimental/metabolism , Mice, Inbred C57BL , Multiple Sclerosis , Th1 Cells/pathologyABSTRACT
Adoptive cell therapy (ACT) is an emerging powerful cancer immunotherapy, which includes a complex process of genetic modification, stimulation and expansion. During these
ABSTRACT
Objective: To evaluate the mechanism of T follicular helper cells ( Tfh ) in experimental autoimmune encephalomyelitis (EAE) via in vivo experiments. Methods:C57BL/6 mice were randomly divided into four groups,CFA group,EAE group,anti-ICOSL group and control group. Lymphocytes of different time points isolated from draining lymph nodes and spleen were stained for T follicular helper cells surface marker and T cells activation surface marker and analyzed by FACS. Observed parameters include inflammatory infiltration,demyelination in spinal cord and germinal center in spleen. ELISA was used to measure the level of antigen specific antibodies. Results: Mice in anti-ICOSL treated group developed mild disease was with lower clinical scores when compared with the EAE group. HE staining results turned out with alleviated inflammation and Luxol Fast Blue staining( LFB) showed no demyelization in anti-ICOSL treated mice compared with non-treated EAE models. Flow cytometry results revealed that percentages of T follicular helper cells decreased though the whole activated degree T cells was not influenced in anti-ICOSL treated group. Fewer ger minal center was found in both anti-ICOSL group and CFA group with reduced secretion of MOG-specific Ab. Conclusion:T follicular helper cells supported the development of cognate B cells,promoted the formation of germinal center,facilitate pathogenic MOG-specific Ab secretion,thus enhance EAE.
ABSTRACT
Objective To characterize CD4+CD8+double-positive T ( DPT) cells in PBMCs from patients with tuberculosis(TB).Methods PBMCs were isolated from peripheral blood samples collected from patients with TB and healthy subjects.The subsets and percentages of CD4+T, CD8+T and DPT cells in PBMCs were determined by flow cytometry.Cell surface markers ( CD45RO, CCR7 and CD25 ) and intracellular cytokines ( IFN-γand TNF-α) were detected directly and after ESAT-6/PPD stimulation.Re-sults Patients with TB showed a significantly increased DPT cells as compared with the cured individuals and healthy subjects (P<0.005).The levels of DPT cells were gradually decreased down to normal upon the treatment of pharmacotherapy.DPT cells expressed higher levet of CD25 than CD4+T and CD8+T cells ( P<0.005 ) . DPT cells could express more IFN-γand TNF-αupon the stimulation of ESAT-6/PPD (P<0.005).The analysis of memory phenotype indicated that DPT cells were memory T cells.Conclusion DPT cells in peripheral blood of the patients with tuberculosis played a critical role in protective immunity against tuberculosis.The alterations of DPT cells in PBMCs during the period of pharmacotherapy might be a potential indicator for the prognosis of pulmonary tuberculosis.