Ahmadi Shadmehri A, Nicknam Mh, Shokrgozar Ma, Mahmoudi M, Sarial Sh, Ahmadi Shadmehri A, Moradi B, Farhadi E, Amirzargar Aa,
Volume 68, Issue 2 (5-2010)
Abstract
Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with presumed autoimmune origin. T cells are considered to play a pivotal role in orchestrating the self-reactive immune responses in multiple sclerosis (MS). This study was performed to investigate the role of polymorphisms of the programmed cell death 1 (PD-1) gene on susceptibility to ankylosing spondylitis.This gene codes an immunoreceptor named PD-1, which has a cytoplasmic domain containing two tyrosine residues located within immunoreceptor tyrosine-based inhibitory and switch motifs (ITIM and ITSM), suggesting that PD-1 is predominantly inhibitory which responsible for the negative regulation in T cell activation and peripheral tolerance. We investigated whether PD-1 gene polymorphism is a genetic modifier for risk and progression of MS.Methods: Blood samples from 150 Iranian Relapsing-Remitting MS patients (mean age,
34.98 years) and 202 healthy controls (mean age, 30 years) were enrolled in this study.The PD-1.3 (7146 G/A Intron 4) and PD-1.9 (7625 C/T Exon 5) polymorphisms were detected by Polymerase Chain Reaction and Restriction Enzyme digestion or Restriction Fragment Length Polymorphism (PCR-RFLP).
Results: No significant association of the mutated alleles with the disease were detected. Because of the ethnic group genetic variation, our data is not like some of
Asian population such as Korea and China.Conclusions: Our data suggest that PD-1 polymorphisms are not act as genetic modifiers of the progression of MS, possibly these polymorphisms don't induce a partial defect in PD-1 mediated inhibition of T-cell activation.
Bahare Hasani Karmozdi , Alireza Mardomi, Saeid Abediankenari,
Volume 79, Issue 8 (11-2021)
Abstract
Background: Mesenchymal stem cells are non-hematopoietic stromal cells that are used in the treatment of many chronic and autoimmune diseases by modulating the immune system. Due to the limitations of using autologous mesenchymal stem cells, the use of allogeneic stem cells is a promising therapeutic approach in the treatment of immunological disorders. This study aimed to investigate the ability of allogeneic mesenchymal stem cells to induce Programmed death-ligand 1(PD-L1) expression on the surface of splenic lymphocytes and the role of this molecule in the mesenchymal stem cell-treated cells tolerogenicity.
Methods: This study was conducted from February 2019 to December 2020 in the department of Immunology of Mazandaran University of medical sciences. Mesenchymal stromal cells were isolated from the femur and tibia of C57 mice. C57 bone marrow-derived mesenchymal stem cells were co-cultured with allogeneic BALB/c splenic cells. After 72 hours, the expression of PD-L1 on the surface of splenic lymphocytes was evaluated by flow cytometry. Interferon-gamma (IFN-γ) and Interleukin-10 (IL-10) cytokine assay were done in the cell culture supernatant. Mesenchymal stem cell-treated BALB/c lymphocytes were then exposed to allogeneic C57 splenocyte as stimuli in the mixed lymphocyte reaction (MLR) and the rate of proliferation was assessed by CFSE.
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Results: The amount of PD-L1 positive BALB/c splenic lymphocytes were significantly increased after allogeneic C57 mesenchymal stem cells exposure (P=0.001). The levels of IFN-γ and IL-10 cytokines in the supernatant of cell culture also increased significantly (respectively, P=0.0009, P=0.01). C57 splenocytes proliferation notably decreased after mesenchymal stem cell-treated BALB/c lymphocytes exposure compared to the group were cultured with naïve BALB/c lymphocytes (P=0.002).
Conclusion: Allogeneic mesenchymal stem cells are capable to induce of PD-L1 on the surface of lymphocytes. PD-L1 expression on mesenchymal stem cell-treated cells makes them less immunogenic than naïve cells. These tolerogenic cells can reduce allogeneic responses. It seems that PD-L1 plays an important role in mesenchymal stem cell immunomodulation
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