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: Regarding the immunomodulatory effects of lactobacillus bacteria, this study aimed to evaluate the effect of oral administration of Lactobacillus reuteri, as probiotic bacteria, on natural killer cell cytotoxicity and tumor-specific lymphocyte proliferation in Balb/c mice with breast adenocarcinoma.

Methods: A total of 30 female mice, aged 6- 8 weeks and with a weight of approximately 17- 19 g, were randomly divided into two groups of 15 mice. The case group received Lactobacillus reuteri at a dose of 2.7× 108 bacteria in half a milliliter of sterile phosphate buffer saline (PBS) and the control group only received PBS. The probiotic group received the regimen for two weeks prior to tumor transplantation, as they did for 30 days after transplantation with three-day intervals and durations of seven days. For the evaluation of natural killer cell cytotoxicity and also tumor-specific lymphocyte proliferation response, LDH and BrdU assays were performed respectively according to the manufacturers' instructions.

Results: The study showed that the mice in the case group which were receiving Lactobacillus reuteri had statistically significant differences in the replication of tumor -specific lymphocytes, natural killer cell cytotoxicity and delayed hypersensitivity responses Compared to the mice in the control group.

Conclusion: Daily consumption of probiotics seems to regulate the immune system and consequently it can be helpful in people with cancer. Moreover, consumption of probiotics in healthy individuals can also boost the efficiency of the immune system against a variety of abnormalities.

---

Background: Immune Thrombocytopenic Purpura (ITP) is an acquired autoimmune disorder characterized by a low platelet count because of anti platelet auto-antibodies. ITP patients have auto antibodies against platelet antigens. T CD4+ lymphocytes are effective cells in immune system that has an important role in auto reactive antibody production and class switching. The pathophisiology and mechanism of ITP is complex and unknown. Numerous studies have difference results about role of T cells in ITP patients. T lymphocytes have been characterized to different subsets. To further investigate about the pathogenesis of ITP, we studied the role of T CD4+ cells and cytokines attributed with platelet count. Therefore, in this research, we evaluated T CD4+ lymphocytes count and interleukin 17 (IL-17), interleukin 11 (IL-11) levels in ITP in comparison with control. Methods: In a case-control study, we have studied 60 patients with ITP and 50 normal individuals as the control group. Peripheral blood mononuclear cells were isolated by ficoll histopaque 1.077. T CD4+ cells count in ITP patients and control subjects were studied by flow cytometry method and serum interleukin 17 (IL-17), interleukin 11 (IL-11) concentration were measured by enzyme-linked immunosorbent assay (ELISA) test. All data were expressed as mean±SD. Differences between means were considered significant at the P< 0.05. Tests were performed using SPSS software version 16. Results: This study showed, T CD4+ cells and plasma IL-17 concentration were not significantly different between patients with ITP and the control group. But plasma IL-11 levels were significantly increased in immune thrombocytopenic purpura patients in comparison with controls (P= 0.031). Conclusion: In summary, our study indicated a role of IL-11 in ITP patients, also showed that ITP may not be associated with changes of plasma IL-17 levels and T CD4+ cells count relative to control population. Therefore, measurement of plasma IL-11 levels may be important criteria in development of ITP. In addition, it is concluded that determination of IL-11 can be a diagnostic marker to recognize thrombocytopenic purpura patients.

---

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.

---

Background: Radiotherapy can cause DNA damage in normal cells, misrepaired or unrepaired double strand breaks in DNA lead to chromosomal breaks. As a result patient experience early and late effects in normal tissue during and after radiotherapy. Cytogenetic techniques can be used as a cancer predictive assay because there is an association between chromosome abnormalities and the risk of developing cancer. Also it can assess patient's complications during the therapy. The aim of the present study was evaluation of the cytogenetic alteration in peripheral blood lymphocytes of esophageal cancer patients treated with radiotherapy. Methods: The present study is an experimental and prospective research. It was done at radiotherapy department at Omid Center in Urmia from January to December 2012. Blood samples were obtained from 15 esophageal cancer patients, before (0 Gy), during (21.6 Gy), and after radiotherapy treatment (43.2 Gy). Blood samples were cultured in RPMI-1640 complete medium containing 1% phytohaemagglutinin and incubated in a CO2 incubator. Cytochalasin-B was added to the cultures at a final concentration of 5 µg/ml. Finally, harvesting, slide making, and analysis were performed according to standard procedures. Results: This study consisted of 15 patients, including 7 men and 8 women from 55 to 84 years old (70.07±11.548). Results indicate that, in the middle of treatment the average frequency of micronuclei increased significantly compared with their concurrent pre-treatment samples (greater than four-fold). Also, an increase in chromosome damage (MN frequency) proportional increasing radiation doses at the end of treatment was observed (P=0.001). Conclusion: Increasing in the MN frequency in the second and third stages is due to radiation effects. Thus, the use of the MN technique for assessing of the side effects in patients during the therapy is very helpful. Moreover, MN assay can be used as a predictive assay for detecting individuals (patient or healthy) with intrinsic radiosensitivity.

---

Background: It is reported that high frequency of chromosomal aberrations in peripheral blood lymphocytes of individuals is a marker of cancer predisposition. The aim of this study was to investigate the in vitro frequency of chromosomal damage in lymphocytes of patients with head and neck cancer against gamma irradiation compared with those in healthy individuals.

Methods: In a case and control study, peripheral blood lymphocytes of 101 patients with head and neck cancer were collected before the onset of radiotherapy. Lymphocytes of 40 healthy individuals were also collected as controls. Head and neck cancer patients and the control group were consecutively recruited between April 2012 and February 2015 from Clinics of Cancer Institute, Imam Khomeini Hospital, Tehran, Iran. Lymphocytes of patients or control group were cultured and exposed to gamma radiation in G2- and G0- phase of the cell cycle. The induced chromosomal aberrations such as chromosome and chromatid breakages, chromosome and chromatid gaps, chromatid exchanges and micronuclei were scored in one-hundred metaphase cells of each individual. The mean of each chromosomal aberration was compared in patient and control groups. Early and late tissue reactions were scored during radiotherapy treatment or thereafter.

Results: There was no significant difference in demographic characterization between the two study groups. The frequency of radiation- induced G2 aberrations in lymphocytes of patients was significantly higher than in those of healthy donors (P= 0.001 for chromosomal breaks). The frequency of radiation-induced micronuclei in G0 assay was also higher in patients than in those in controls (P= 0.05). The results also indicate that there is no correlation between the two assays. No significant correlation was also observed between aberration frequencies in lymphocytes and the degree of both early and late normal tissue reactions.

Conclusion: The results indicate that the in vitro chromosomal radiosensitivity of peripheral blood lymphocytes of patients with head and neck cancer against gamma irradiation was significantly higher than that in healthy individuals.