Tehran University Medical Journal

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.

Background: Multiple Sclerosis (MS) is an autoimmune disease with impairment in function of central nervous system. Macrophages and dendritic cells play important roles in alleviating or progression of the disease. These cells can cause inflammation and damage to the myelin of nerve cells by realizing of harmful substances when these cells get matured. We studied the effect of Alternaria alternata extract on maturation of monocyte- derived dendritic cell (modc) and T-cell responses in the presence of Myelin Basic Protein (MBP) as a laboratory model of multiple sclerosis (MS). The purpose of this study is suitable dendritic cells production for usage in MS immunotherapy.
Methods: For this study plastic adherent monocytes were cultured with granulocyte/ macrophage- colony stimulating factor (GM-CSF) and interleukin -4 for converting these cells to modc and pulsed with MBP and matured in the presence of monocyte-conditioned medium (MCM) in control group and MCM + Alternaria alternata extract in treatment groups. Anti-CD14, anti-CD83, anti-human leukocyte antigen-DR (anti HLA-DR) monoclonal antibody were carried out for phenotyping. Autologos T cell responses and cytokine production were evaluated.
Results: The results showed that the expression of CD14 decreased and CD83, HLA-DR increased in treatment groups in comparison with control groups. The production amount of IL-10 overcame IL-12 and in T cell the production of cytokines, IL-17 and Interferon-γ (IFN-γ) decreased and IL-4 was increased (P<0.05). These effects escalated with increasing of dosage from 50 to 100 (mg/ml) (P<0.001).
Conclusion: Alternaria alternata extract can cause maturation of MBP-pulsed modc and skewing of T- lymphocyte toward Th2 and thereby can evolve into a new strategy in immunotherapy of MS.