Tehran University Medical Journal

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Dendritic Cell (DC) is an important antigen-presenting cell that present tumor antigen to CD8⁺ and CD4⁺ T- Lymphocytes and induce specific anti-tumor immunity. In order to induce effective anti-tumor response, an option is increasing the efficiency of antigen presentation of dendritic cells and T cell activation capacity. The aim of the present study was to investigate the effect of dendritic cell maturation with protein components of toxoplasma gondii on cytotoxic T lymphocyte activity and their infiltration in to the tumor.
Methods: For DC generation, bone marrow cells were cultured in the presence of GM-CSF and IL-4 for five days. After that, LPS, protein components and whole extract of toxoplasma gondii were added to the culture media and incubated for another two days for DC maturation. To generate tumor, mices were injected subcutaneously with WEHI-164 cell line. For immunotherapy 10⁶ DCs matured with different compounds were injected around the tumor site. Infiltration of CD8⁺ T cells were determined by flow cytometry and cytotoxic activity was measured by LDH detection kit.
Results: Immunotherapy with DCs treated with protein components of toxoplasma gondii led to a significant increase in the activity of cytotoxic T cells and infiltration of CD8⁺ T cells in to the tumor. Immunotherapy using protein components of toxoplasma gondii significantly improved the survival of the mice compared with other groups (p<0.0001).
Conclusion: Protein components of toxoplasma are able to increase DC capability in induction of CTL-mediated anti-tumor response and increase infiltration of these cells in to the tumor.

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Mesenchymal Stem Cells (MSCs) are well known as the regulator of the immune system. These multipotent non-hematopoietic progenitor cells have been originally isolated from bone marrow, and later on found in several other tissues, such as skeletal muscle, umbilical cord blood, adipose and fetal liver tissues. Immunomodulatory effects of MSCs on a variety of immune cells such as T and B lymphocytes, Natural Killer cells (NK), neutrophils, macrophages and dendritic cells, has made a good candidate of them for the treatment of inflammatory disorders, particularly autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. In addition, several studies have indicated mechanisms by which MSCs could reduce immune cell proliferation and activation leading to immune tolerance induction. Since T lymphocytes are considered as the most important immune cells, effect of MSCs on the activity of these cells has a very special significance to direct immune response. Under various conditions, T-lymphocytes have different phenotype and performance and can be differentiated into particular subtype such as regulatory T cells. Both in vitro and in vivo studies have indicated that MSCs modulate innate and adaptive immune system by promoting generation of CD4+CD25+ T regulatory cells which have important role in immune tolerance induction and autoimmune disease prevention. MSCs are able to block pro-inflammatory and increase anti-inflammatory cytokines secretion. So such unique immunomodulatory features make MSCs ideal candidates for clinical application as immunosuppressants which can be considered for autoimmune diseases treatment. Therefore, in this short-review, we attempt to focus mainly on the existing information about MSCs in association with immunomodulatory function of them on the immune system. In addition, the possible mechanisms and the performance impact of MSCs in autoimmune diseases improvement are discussed here. However, increasing knowledge of how MSCs will influence on the immune system suppression, leading us to better use of these cells as a promising tool in the treatment of autoimmune diseases.