Iranian journal of immunology
Volume:12 Issue: 1, Winter 2015

To assess the effect of tumoral ASCs on the trend of regulatory T cells differentiation. Peripheral blood naïve CD4+ T cells were co-cultured with ASCs derived from breast cancer or normal breast tissues. In separate cultures peripheral blood naïve CD4+ T cells were exposed to the culture supernatants of ASCs. Generation of CD4+CD25+Foxp3+ and CD4+CD25-Foxp3+ Treg subsets was observed after coculture of naïve CD4+ T cell with either ASCs or the related supernatant. The percentage of CD4+CD25+Foxp3+ cells increased after exposing naïve CD4+ T cells to both ASCs and theirsupernatants while augmentation of CD4+CD25-Foxp3+ subset mostly depended on the presence of ASCs. Similarly, upregulation of FoxP3 molecule was more significant in condition of cell to cell contact. IL-4 and IL-10 were up-regulated in the cocultured naïve CD4+ T cells after exposure to ASCs/supernatant while IFN-γ was down-regulated in the presence of ASCs. ASC may act as one of the major players in tumor site with immunomodulatory effects, which may mostly be carried out through direct cell-cell interaction. Razmkhah M, et al. Iran J Immunol. 2015; 12(1):1-15

Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cell transplantation (HSCT), used in Leukemia treatment. CD26+ cells, a fraction of CD34+cells, are a major population of UCB cells which negatively regulate the in vivo homing and engraftment of HSCs. CD26 is highly expressed in various cells such as HSCs, immune cells, fibroblasts, and epithelial cells. It has been shown that the inhibition of the CD26 on CD34+ cells improves the efficiency of Hematopoietic Stem and Progenitor Cell (HPC) transplantation.

To evaluate the relationship between the production of B, T, and NK cells from the CD26 positive fraction of cord blood mononuclear cells.

Cord blood mononuclear cells were cultured for 21 days using different combinations of stem cell factors (SCF), Flt3 ligand (FL), IL-2, IL- 7, and IL-15. The harvested cells were then analyzed by flowcytometry every week for 21 days.

T cell differentiation from CD26 subset of cord blood mononuclear cells increased by using IL-2 and IL-7. Our data showed that IL-2 and IL-7 significantly affected the generation of B cells from CD26+ cord blood mononuclear cells. On the other hand, NK (NKp46+) derived CD26+ cells increased by IL-15 and IL-2.

Taking all into account, we conclude that B, T, and NK cells can differentiate from the CD26+ subset of mononuclear cord blood cells by using key regulatory cytokines.

Herpes simplex viruses (HSV) are human pathogens that establish lytic and latent infections. Reactivation from latency occurs intermittently, which represents a lifelong source for recurrent infection. The role of immune factors in the control of recurrent symptomatic HSV lesions is complex and the exact role of cytokines remains unclear. To assess the levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL- 10) along with anti-herpetic IgG and IgM, in the symptomatic reactivation of HSV infection. Thirty-six patients with recurrent symptomatic herpes infection were selected as the study group and thirty-two healthy individuals with no history of symptomatic labial herpes infection enrolled as the control group. Skin swabs were obtained from lip and skin lesions for viral culture. Confirmation of HSV cytopathic effect was carried out using PCR assay. The levels of TNF-α, IL-10, IgG and IgM were measured using ELISA. The level of TNF-α was significantly lower in individuals with recurrent symptomatic herpes infection in comparison with the controls (p=0.04). Also a significant elevation was observed in the levels of specific IgG in patients compared to controls (p<0.05). The decreased level of TNF-α and increased levels of IgG in individuals with a history of symptomatic reactivation of HSV infection is suggestive of a probable shift in favor of the Th2 immune response.

It has been reported that vitamin D has broad anti-inflammatory and immunomodulatory effects. To evaluate the effects of vitamin D on the expression of IL-27 and IL-33 in a model of experimental autoimmune encephalomyelitis (EAE). EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein mixed with complete Freund's adjuvant. The mice were administered with PBS or olive oil, intraperitoneally, in the control groups and vitamin D (200 ng every two days) in the treatment group, from day +3 to +30. At day 31, the mice were scarified and their spinal cords and brains were harvested. The expression of the IL-27 and IL-33 mRNA in the spinal cord wasmeasured using real time-PCR. In PBS- or olive oil-treated EAE mice the expression of IL-27 P28 mRNA was significantly lower than that in the healthy control group (p<0.002). In both PBS- and olive oil-treated EAE groups, the expression of IL- 27 EBI3 mRNA was also lower than that observed in the healthy group, but the differences were not significant. In vitamin D-treated EAE group, the expression of IL- 27 P28 and IL-27 EBI3 were significantly higher compared with the olive oil-treated EAE groups (p<0.002 and p<0.04, respectively). The expression of IL-33 was significantly higher in PBS-or olive oil-treated EAE groups compared with healthy mice (p<0.05 and p<0.02, respectively). Vitamin D significantly decreased the expression of IL-33 compared with PBS- or olive oil-treated EAE mice (p<0.04, p<0.02, respectively). The PBS- or olive oil-treated EAE mice showed the clinical symptoms of EAE at days 9 and 10, respectively. The vitamin D-treated EAE group exhibited the symptoms at day 12 post immunization. The maximum mean clinical score and mean pathological scores were also significantly lower in vitamin D-treated EAE group, in comparison with PBS- or olive oil treated EAE mice (p<0.001). Vitamin D may modulate the expression of IL-27 and IL-33 in the spinal cord of EAE mice and also ameliorate the clinical symptoms of the disease.

Differentiation between the muscularis mucosae (MM) and muscularis propria (MP) of the bladder remains challenging. To identify MM- and MPspecific antigens that could be of potential value for staging of urothelial carcinoma in a pilot study. The expression of 12 protein antigens in 11 human bladder specimens was examined. There were 5 post radical cystectomy specimens and 6 normal bladder autopsy specimens. Antibodies against actin, caldesmon, type IV collagen, cytokeratin, desmin, elastin, fibronectin, filamin, laminin, miotilin, smoothelin, and vimentin were used. Slides were stained with immunohistochemical reagents and assessed using light microscopy. The intensity of the immune reaction within MM and MP was evaluated in a four-level scale as negative and weakly, moderately or strongly positive. The presence of MM was noticed in 63.6% of specimens. The expression of desmin, filamin, and smoothelin was stronger within MP compared to MM in all cases. Stronger reaction with anti-type IV collagen antibodies was noticed within MP in 80% of the cases. In the whole study group, the expression of vimentin was stronger within MM than MP. MM and MP cells are of different antigenic characteristics. This can be used in the microscopic diagnostics of selected cases. The results need to be validated in a series of specimens from transurethral resection.

T-2 mycotoxin belongs to the Trichothecene family and has damaging effects on the immune system. To investigate the toxic effect of T-2 toxin on the percentage of peripheral blood B lymphocytes and the potential protective role of selenium and vitamin E. Frequencies of B lymphocytes (CD19+) were analyzed after injection of sublethal doses of T-2 toxin into Balb/c mice at different time points, using flowcytometry. Additionally, the effects of selenium and vitamin E on B lymphocyte, as either prophylaxis or simultaneously administered with T-2 toxin, were investigated. After injection of a sublethal dose of T-2 toxin, the number of B cells (CD19+) significantly decreased at 12 h and became normal at 72 h. When selenium was injected both 24 h before and simultaneously with T-2 toxin, it was able to inhibit B lymphocyte (CD19+) reduction. In contrast, injecting vitamin E, 24 h before or simultaneously with T-2 toxin did not regulate B lymphocyte alteration. Selenium plays pivotal role on altered B lymphocyte subset induced by T-2 toxin comparing to vitamin E.

Bacillus Calmette-Guérin (BCG) vaccination is recommended for newborn infants worldwide to prevent tuberculosis. However, complications do occur inevitably in a very low rate, among which the most serious is disseminated disease. The disseminated bacillus Calmette–Guérin disease is a rare disease with high fatality, and can be seen among persons with an underlying immunodeficiency. We report a 4-month-old male infant presenting with recurrent fever, an isolated left axillary mass and swelling at the site of BCG inoculation. The cellular immune function analysis showed that the value of CD4/CD8 was 0.994, indicating the existence of immunodeficiency. The results of blood culture and throat swab culture showed conditional pathogen infection. He died of cardiopulmonary failure. In this case, necropsy played a significant role in the final diagnosis of disseminated pulmonary tuberculosis.

Celiac disease is a common autoimmune disorder that is diagnosed based on clinical case identification, serological screening, and duodenal histology. However, the existence of mild clinical forms, such as seronegative cases with patchy atrophy and potential celiac disease, can make it difficult to determine a definitive diagnosis. The seronegative patients with celiac disease can include those with discordant antibody results and false-negative results, due to unknown origins or selective IgA deficiency. We present two cases with discordant antibody results in order to evaluate if the simultaneous detection of specific antibodies can improve the serodiagnosis of celiac disease. In both patients, the simultaneous detection of IgA/IgG anti-tissue transglutaminase/deamidated gliadin peptides gave discordant positive results by the same antibodies assayed individually. Although further studies are needed to confirm and extend our findings, the simultaneous detection of specific antibodies seems to improve the serodiagnosis of celiac disease in patients with discordant antibody results.