Immunity phenomena following olfactory ensheathing cell transplantation into experimental allergic encephalomyelitis rat brain

Olfactory ensheathing cells （OECs） can promote axonal regeneration and remyelination for the treatment of spinal cord injury. OECs can also treat experimental allergic encephalomyelitis （EAE）, but it remains unclear whether OECs might be rejected by the immune system in the brain including the destruction of the blood-brain barrier under inflammation, the release of inflammatory factors, the activation of local antigen-presenting cells （e.g., microglia cells） and antigen drainage. We found that OECs expressed major histocompatibility complex （MHC）-I molecules on the cell surface, barely expressed MHC-II, but MHC-II could be induced by interferon-v, suggesting that OECs have certain immunogenicity. When OECs were transplanted into normal animal brains, no OECs were phagocytosed by dendritic cells in the cervical lymph node, and OECs did not induce lymphocyte proliferation, which indicates that OECs share some immune privilege under normal conditions. However, OECs in the rat EAE brain were phagocytosed by dendritic cells in the cervical lymph node and enhanced lymphocyte proliferation. These findings suggest that OECs are rejected because of increased immunogenicity in EAE brain, and that brain inflammation, in particular activated dendritic cells, may be a prerequisite for rejecting OECs.

Role of mesenchymal stem cell derived extracellular vesicles in autoimmunity: A systematic review

BACKGROUND Mesenchymal stem cells(MSCs)have been reported to possess immune regulatory effects in innate and adaptive immune reactions.MSCs can mediate intercellular communications by releasing extracellular vesicles(EVs),which deliver functional molecules to targeted cells.MSC derived EVs(MSC-EVs)confer altering effects on many immune cells,including T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages.A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases.This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases.AIM To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases.METHODS Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language.The keywords,such as“MSCs,”“EVs,”“exosome,”“autoimmunity,”“tumor immunity,”and“transplantation immunity,”and Boolean operator“AND”and“NOT”coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases.Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded.RESULTS A total of 96 articles were chosen for final reference lists.After analyzing those publications,we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells,like T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages,to regulate immune responses in innate immunity and adaptive immunity.Many validated EVsdelivered molecules have been identified as key biomarkers,such as proteins,lipids,and nucleotides.Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease.CONCLUSION MSC-EVs play an equally important part in the differentiation,activation,and proliferation of immune cells,and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.

Bone marrow stromal cell line co-transfected with IL-2 and IL-3 genes can accelerate restoration of T-cell immunity in allo-BMT mice

Background After T-cell depleted allogeneic bone marrow transplantation, impaired immune reconstitution is a major cause of morbidity and mortality in the recipient The purpose of this study was to observe the effects of the gene-engineered bone marrow stromal cell line QXMSC1-IL-2+IL-3 on the reconstitution of T-cell immunity in allo-BMT mice Methods The bone marrow stromal cell line QXMSC1 was co-transfected with IL-2 and IL-3 genes using a Tet-on gene expression system T lymphocyte subset counts per spleen were analyzed by flow cytometry Lymphocyte proliferation response to ConA was examined to evaluate T-cell function CDR3 spectratyping techniques were performed to evaluate TCR repertoire diversity at various time points post-transplantation Results Gene engineered bone marrow stromal cell line QXMSC1-IL-2+IL-3 could express IL-2 and IL-3 (1300 ng·day -1 ·10 -6 cells and 1100 ng·day -1 ·10 -6 cells, respectively) under the control of doxycycline QXMSC1-IL-2+IL-3 in combination with allogeneic bone marrow could significantly increase the counts of CD4 + and CD8 + T cell, 1.72 and 1.27-fold respectively at week 3 compared with TCD-BMT group ( P <0.01); make CD4 +/CD8 + ratio return to normal level at week 4; enhance splenocytes mitotic response to ConA ( P <0.01), and accelerate restoration of TCR repertoire diversity in the lethally irradiated mice ( P <0.05) KH*2/5DConclusion The gene transduced stromal cell line QXMSC1-IL-2+IL-3 is able to accelerate T-cell immunity in allo-BMT mice

Immature CD4＋ dendritic cells conditioned with donor kidney antigen prolong renal allograft survival in rats

Background AIIogeneic transplant rejection is currently a major problem encountered during organ transplantation. The dendritic cell （DC） is the most effective powerful known professional antigen-presenting cell, and recent studies have found that DCs can also induce immune tolerance, and avoid or reduce the degree of transplant rejection. The aim of this study was to evaluate the effect of transfused immature CD4~ DCs on renal allografts in the rat model. Methods In this study, we induced CD4~ immature DCs from rat bone marrow cells by a cytokine cocktail. The immature CD4~ DCs were identified by morphological analysis and then the suppressive activity of these cells conditioned with donor kidney antigen was evaluated in vitro and in vivo. Results Immature CD4~ DCs conditioned with donor kidney antigen possessed immunosuppressive activity in vitro and they were able to prolong renal transplant survival in an allograft rat model in vivo. Conclusions Our study provides new information on efficacious renal transplantation, which might be useful for understanding the function of immature CD4~ DCs in modulating renal transplant rejection and improving clinical outcome in future studies.

Study on blocking the leukemia immune escape after BMT by Fas-Fas ligand pathway

Background To investigate if bone marrow transplantation (BMT) with bone marrow mononuclear cells (BMMCs) transducted with murine soluble Fas gene (sFas) using adenovirus vector could block the immune escape of leukemia cells eliminate the residual leukemia cells and reduce their relapse.Methods The recombinant adenovirus vector with murine sFas, adsFas, and the control vector adEGFP were constructed using homologous recombination between two plasmids in Escherichia coli. BMT was carried out after the BMMCs were infected with Adenoviruses. The mice models of leukemia/lymphoma were constructed by inoculating female C57BL/6 mice (H-2 b) with 10 5 EL4 cells/mouse through caudal vein. Donors of bone marrow grafts were syngeneic male mice. BMMCs were infected with AdsFas or AdEGFP 24 hours before (Group D or E). The following three groups were simultaneously used: Group A, no BMMCs transplanted; Group B, transplanted with BMMCs not infected with adenoviruses; Group C, only transfusing EL4 cells, neither irradiation nor BMT. The hematopoietic reconstitution, generation of leukemia/lymphoma and the survival rate were observed in all groups after BMT. Results The adenovirus vectors were successfully constructed. The titre of virus after purification was up to 2.5×10 11 pfu/ml. Spleen indices examined 11 days after BMT were not obviously different among Group B, D and E (P>0.05), but indices in Group A were significantly lower than those in the latter three groups (P<0.01). Counts of leukocytes and platelets on +30 day showed mice were reconstituted satisfactorily in Group B and D, but very low in Group C and E. The Y-chromosomes existed 2 months after BMT and examination of bone marrow cytology showed that Group B and D were almost normal, but Group C and E had plenty of lymphoblast-like tumor cells. Tumors were obviously observed in the mice of Group C and E by histopathological examination, but the mice in Group B and D were normal. The survival rates were 0 (0/4) in Group A, 100% in Group B (6 /6) and D (16/16), 12.5% (2/16) in Group C and 6.25% (1/16) in Group E respectively. It is demonstrated that, in contrast with the control (Group EGFP), surviv al rate was significantly increased in the sFas Group (P<0.01). Conclusions The transfer of sFas gene by adenovirus changed the prognosis state of leukemia/lymphoma mice after auto-BMT. The transduction of sFas might block the effect of the immune escape of EL4 cells through FasL. These results could thus provide a new direction to find a way to treat the leukemia and its recurrence after BMT.