Regulatory T Cell Subtypes and TGF-β1 Gene Expression in Chronic Allograft Dysfunction
Sara
Assadiasl
Department of Immunology, School of Medicine
author
Pedram
Ahmadpoor
Chronic Kidney Disease Research Center, Labbafinejad Hospital, Shahid
Beheshti University of Medical Sciences
author
Mohsen
Nafar
Chronic Kidney Disease Research Center, Labbafinejad Hospital, Shahid
Beheshti University of Medical Sciences
author
Mahboob
Lessan Pezeshki
Nephrology Research Center, Tehran University of Medical
Sciences
author
Fateme
Pourrezagholi
Chronic Kidney Disease Research Center, Labbafinejad Hospital, Shahid
Beheshti University of Medical Sciences
author
Mahmoud
Parvin
Department of Pathology, Labbafinejad Hospital, Shahid Beheshti University of Medical
Sciences, Tehran, Iran
author
Abtin
Shahlaee
Molecular Immunology Research Center, Tehran
University of Medical Sciences
author
Adel
Sepanjnia
Department of Immunology, School of Medicine
author
Mohammad Hossein
Nicknam
Department of Immunology, School of Medicine
author
Aliakbar
Amirzargar
Department of Immunology, School of Medicine
author
text
article
2014
eng
Background: Regulatory T cells have been suggested to have a protective role against acute rejection in allograft recipients. However, there is little information available about their contribution to chronic rejection process. The role of transforming growth factor-beta 1 (TGF- β1) as a profibrogenic and/or immunoregulatory cytokine in renal allografts is also controversial. Objectives: To evaluate the frequency of CD4+CD25+CD127- and CD3+CD8+CD28- regulatory T cells in chronic allograft dysfunction (CAD) and to investigate the expression of TGF- β1 in renal allografts. Methods: Thirty biopsy-proven CAD patients were pair-matched with 30 stable graft function patients and a third group of healthy volunteers. Flowcytometry was performed on PBMCs to determine the frequency of CD3+CD8+CD28- and CD4+CD25+CD127- regulatory T cells in lymphocyt population. TGF- β1 gene expression was assessed by Real Time PCR. Results: The percentage of CD3+CD8+CD28- Tregs among renal allograft recipients was higher than healthy controls (p<0.001) since stable graft patients showed the most rates. The frequency of CD4+CD25+CD127- Tregs was lower in CAD patients than stable recipients (p=0.024) and healthy group (p=0.015). TGF- β1 gene expression was greater in CAD patients compared to healthy group (p=0.03) but there was no significant difference between gene expression of stable graft patients and healthy volunteers. Conclusion: The negative association between the frequency of regulatory T cell subtypes and chronic allograft dysfunction proposes these cells as probable candidates for promoting allograft survival. Moreover, despite the immunoregulatory capacity of TGF- β1, it is likely to be implicated in chronic damages of allograft tissue.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
11
v.
3
no.
2014
139
152
https://iji.sums.ac.ir/article_16775_55ff8f8fc06faf95c2f270f4622a0b6f.pdf
Maturation State and Function of Monocyte Derived Dendritic Cells in Liver Transplant Recipients
Afsoon
Shariat
Department of Biology, College of Basic Sciences, Tehran Science and Research Branch, Islamic Azad
University, Tehran
author
Mohammad Hossein
Karimi
Shiraz Transplant Research Center, Namazi Hospital, Shiraz University of Medical
Sciences, Shiraz
author
Talat
Mokhtariazad
Department of Virology, School of Public Health, Tehran University of Medical
Sciences,
author
Seyed Mohammad
Moazzeni
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modarres University, Tehran
author
Bita
Geramizadeh
Shiraz Transplant Research Center, Namazi Hospital, Shiraz University of Medical
Sciences, Shiraz
author
Seyed Ali
MalekHosseini
Shiraz Transplant Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
author
Ramin
Yaghobi
Shiraz Transplant Research Center, Namazi Hospital, Shiraz University of Medical
Sciences, Shiraz
author
text
article
2014
eng
Background: Dendritic cells (DCs) are potent antigen presenting cells for triggering of the immune reaction post transplantation. These cells are centrally involved in the initiation of T cell-dependent immune responses. Objective: To compare the level of DC maturation and function in liver transplant recipients with healthy controls. Methods: In this study, twelve peripheral blood samples were selected from six liver transplant patients and six healthy controls. After the generation of DCs from monocytes, expression levels and mean fluorescent intensity (MFI) of several DC maturation markers were evaluated using flowcytometry. Secretion of IL-6, IL-12 and IL-23 proinflammatory cytokines was determined using ELISA. Gene expressions of TLR-2, TLR-4 and IL-23 were analyzed using real-time PCR. Results: DC expression markers including CD83 (p=0.007) and CD86 (p=0.02), as well as secretion of IL-6 (p=0.02) and IL-12 (p=0.007) by DCs were significantly increased in liver transplant patients compared with healthy controls. The MFI of CD86 (p=0.009) and HLA-DR (p= 0.005) expression on DCs was also higher in patients. The expression of TLR-2 transcripts in DCs of patients was higher than that of the controls (p=0.03). Conclusion: Based on these findings, increased frequency of DCs expressing CD83 and CD86, higher expression of CD86, HLA-DR, and TLR-2 as well as elevated secretion of proinflammatory cytokines in DCs of liver transplant recipient's point to the more mature phenotype and active function of DCs in patients compared with controls.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
11
v.
3
no.
2014
153
165
https://iji.sums.ac.ir/article_16776_fbc01a4357272d4ac0222c8fece6673b.pdf
Optimizing Dendritic Cell Preparation for Fusion with Melanoma Cells
Yang
Li
Department of Orthopaedics
author
Lu
Zhang
Department of Maternity, First Affiliated Hospital, Dalian Medical University,
Dalian, Liaoning Province, China
author
Shouyu
Wang
Department of Orthopaedics
author
Peng
Shi
Department of Orthopaedics
author
Wei
Qu
Department of Orthopaedics
author
text
article
2014
eng
Background: Fusion of dendritic cells (DCs) with melanoma cells could reinforce the antigenicity of tumors as a strategy for the treatment of malignant melanoma. However, the insufficient quantity of DCs and the low fusion efficiency limits the development of such approach. Objective: To define the dosage of the stimulating factors as well as the induction condition for the optimal DCs preparation and cell fusion. Methods: DCs were generated from murine bone marrow cells, and cultured with four different concentrations of the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). DCs were confirmed to be mature by detecting the expression of MHC-II, CD11c, CD80, and CD83 by flowcytometry. DCs-melanoma fusion cells were generated using polyethylene glycols (PEG) with different molecular weights and the fusion efficiency was detected by fluorescence-activated cell sorter (FACS). Results: The largest quantity of DCs was found when cells were cultured with 1000 U/ ml of GM-CSF and 500 U/ml of IL-4 (1.69 ± 0.04 ×10 6 ml-1, p<0.001 when compared with the other three groups). The expression levels of MHC-II and CD83 on day 7 after incubation were significantly lower than those on day 3 (MHC-II: p<0.001; CD83: p<0.001). The efficiency of cell fusion under induction of PEG-3000 was significantly higher than that of PEG-4000 (15.4 ± 0.56% vs. 11.1 ± 0.45%, p<0.001). Conclusions: The largest quantity for mature DCs was stimulated with 1000 U/ml of GM-CSF and 500 U/ml of IL-4 and the highest fusion efficiency was under induction of PEG-3000.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
11
v.
3
no.
2014
166
176
https://iji.sums.ac.ir/article_16777_2cf205cd44b640d932bc1c4244780818.pdf
Immunomodulatory Effects of Mice Mesenchymal Stem Cells on Maturation and Activation of Dendritic Cells
Ladan
Sadeghi
Department of Biology, Islamic Azad University, Fars Science and Research Branch
author
Eskandar
Kamali-Sarvestani
Autoimmune
Diseases Research Center and Immunology Department, Shiraz University of Medical Sciences
author
Negar
Azarpira
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz
author
Mehrdad
Shariati
Department of Biology,
Islamic Azad University, Kazerun branch, Kazerun, Iran
author
Mohammad Hossein
Karimi
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz
author
text
article
2014
eng
Background: Mesenchymal stem cells (MSCs) possess a wide range of immunomodulatory functions mostly in immune cells including dendritic cells (DCs). DCs are the key cells in the immune response and play an important role in initiating cell-mediated immunity. Objective: To evaluate the immunomodulatory effects of MSCs supernatant on maturation and function of DCs. Methods: Bone marrow derived mice MSCs were isolated and cultured. Twenty-four, forty-eight and seventy-two hours after passage 6, supernatants were collected and MSCs were assessed by cytometric analysis for the expression of CD34, CD44, CD45 and SCA-1. Splenic DCs were isolated using MACS and then co-cultured with MSCs supernatant. Expression of CD86, CD40 and MHC-II on DCs were also evaluated by cytometry. H 3-thymidine incorporation by proliferating T cells was determined in two separate MLR assay settings. In one setting, DCs were co-cultured with T cells in the presence of MSCs supernatant, and in the other setting DCs were treated with MSCs supernatant and then were co-cultured with T cells. Production of IL-12, IL-6 and IL-10 cytokines was measured in the supernatant of DCs treated with MSCs supernatant. We also measured IFN- γ and IL-4 levels in MLR supernatant. Results: The results showed that 72h MSCs supernatant could decrease the expression of MHC-II and CD86. The T cell proliferation was inhibited in the presence of MSCs supernatant and MSCs supernatant treated DCs as demonstrated by MLR assay. A significant increase in IL-4 level and a non significant decrease in IFN- γ level in MLR supernatant were observed. However, IL-6, IL-10 and IL-12 production did not change significantly. Conclusion: MSCs supernatant has a time dependent effect on the maturation of DCs. Also, it could alter cytokine production from responding T cells toward Th2. Generally, the findings of this study supported the immunomodulatory effect of MSCs supernatant on DCs maturation and function.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
11
v.
3
no.
2014
177
188
https://iji.sums.ac.ir/article_16778_55c9f0634f03d545f6a1e70d4898ddd7.pdf
Improved Immunogenicity of Tetanus Toxoid by Brucella abortus S19 LPS Adjuvant
Mohsen
Mohammadi
Immunology Lab, Institute of Biochemistry and Biophysics, University of Tehran
author
Zahra
Kianmehr
Immunology Lab, Institute of Biochemistry and Biophysics, University of Tehran
author
Sussan
Kaboudanian Ardestani
Immunology Lab, Institute of Biochemistry and Biophysics, University of Tehran
author
Behnaz
Gharegozlou
Faculty of Allied Health,
Department of Immunology, Tehran University of Medical Science, Tehran, Iran
author
text
article
2014
eng
Background: Adjuvants are used to increase the immunogenicity of new generation vaccines, especially those based on recombinant proteins. Despite immunostimulatory properties, the use of bacterial lipopolysaccharide (LPS) as an adjuvant has been hampered due to its toxicity and pyrogenicity. Brucella abortus LPS is less toxic and has no pyrogenic properties compared to LPS from other gram negative bacteria. Objectives: To evaluate the adjuvant effect of B. abortus (vaccine strain, S19) LPS for tetanus toxoid antigen (TT) and to investigate the protective effect of different tetanus vaccine preparations. Methods: LPS was extracted and purified from B. abortus S19 and KDO, glycan, phosphate content, and protein contamination were measured. Adipic acid dihydrazide (ADH) was used as a linker for the conjugation of TT to LPS. Different amounts of B. abortus LPS, TT, TT conjugated with LPS, and TT mixed with LPS or complete Freund’s adjuvant (CFA) were injected into mice and antibody production against TT was measured. The protective effect of induced antibodies was determined by LD50. Results: Immunization of mice with TT+LPS produced the highest anti-TT antibody titer in comparison to the group immunized with TT without any adjuvant or the groups immunized with TT-LPS or TT+CFA. Tetanus toxid-S19 LPS also produced a 100% protective effect against TT in immunized mice. Conclusion: These data indicate that B. abortus LPS enhances the immune responses to TT and suggest the possible use of B. abortus LPS as an adjuvant in vaccine preparations.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
11
v.
3
no.
2014
189
199
https://iji.sums.ac.ir/article_16779_56cb942d97014159cdd4f8f131ba8eaa.pdf
Serum TNF-α, IL-10 and IL-2 in Schizophrenic Patients Before and After Treatment with Risperidone and Clozapine
Abolghasem
Ajami
Molecular and Cell Biology Research Center
author
Farshideh
Abedian
Department of Immunology
author
Seyyed Hamzeh
Hosseini
Psychiatry Research Center
author
Elahe
Akbarian
School of Medicine, Mazandaran University of Medical Sciences, Sari
author
Reza
Alizadeh-Navaei
Molecular and Cell Biology Research Center
author
Mehrdad
Taghipour
Urology and Nephrology
Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
author
text
article
2014
eng
Background: Schizophrenia is a disorder of the executive function of both sensory and central nervous system. Recent studies suggest that immune mechanisms play a role in the pathophysiology of this disease. The variations in cytokine concentrations have been associated with psychopathology and treatment of schizophrenia. Objective: To investigate the changes in serum concentrations of TNF- α, IL-10, and IL-2 in schizophrenic patients before and 40 days after treatment. Methods: In a case-control study, 26 schizophrenic patients and 26 healthy individuals were enrolled as the control group. PANSS scale questionnaire was used for diagnosis and assessing the severity of the disease. All patients were then treated with risperidone or clozapine for 40 days. Serum concentrations of TNF- α, IL-10 and IL-2 were measured by ELISA before and after treatment in both groups. Paired t-test and Independent t-test were used for comparison of data. Results: Comparison of TNF-α and IL-10 concentrations in patients before and after treatment revealed a significance decrease of TNF- α and increase of IL-10 concentrations (p=0.002, and p=0.008, respectively). Serum concentrations of IL-2 were lower than the detection limit of assay and were not detectable. In comparison with healthy controls, serum concentrations of TNF- α in schizophrenic patients were higher, while IL-10 concentrations were lower before treatment although the differences were not significant (p=0.291 and p=0.375, respectively). There was no correlation between cytokine concentrations and the positive and negative scale (PANSS). Also no significant difference in the admission, relapses, and duration of illness before and after treatment was observed. Conclusions: Increase of TNF- α and decrease of IL-10 may have an important role inpsychopathology of schizophrenia.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
11
v.
3
no.
2014
200
209
https://iji.sums.ac.ir/article_16780_d0da28f52eaa43672769b4523072cd28.pdf
Correlation between Salivary Toll Like Receptor-2 Concentration and Early Childhood Caries
Beheshteh
Malekafzali
Dental Research Center, Research Institute of Dental Sciences
author
Mandana
Sattari
Department of Immunology, School of
Medicine
author
Sanaz
Keyvanfar
Department of Pediatric Dentistry, School of Dentistry, Shahid Beheshti University of Medical
Sciences, Tehran, Iran
author
text
article
2014
eng
Background: Early childhood caries (ECC) is a common health problem in the developing countries. Basic knowledge about the etiology and pathogenesis of ECC plays an important role in its prevention. Objective: To determine the relationship between salivary TLR-2 concentration and early childhood caries formation Methods: Twenty-Eight children with ages ranging from 36 to 71 months (15 in ECC group and 13 in caries free group) were chosen based on inclusion criteria. Their saliva was aspirated in the volumes of 1-2 ml. Resampling was done for 8 subjects of ECC group 3 months after dental restoration. TLR-2 concentration was measured using ELISA. Results: Mean concentrations of TLR-2 in ECC and caries free group were 2.12 and 1.42 ng/ml, respectively. The difference between concentrations was statistically significant (p=0.008). Three months after treatment in 8 ECC, the mean concentration of TLR-2 (0.925 ng/ml) significantly decreased compared to the original concentration in ECC (p<0.001) and caries free groups (p<0.001). Conclusion: Elevated concentration of TLR-2 in ECC group compared to caries free group and its decrease after treatment point to the participation of innate immune system and specially TLR-2 in the pathogenesis of early childhood caries.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
11
v.
3
no.
2014
210
216
https://iji.sums.ac.ir/article_16781_8c7c57e3c442e49cff0c18d3cea1c250.pdf
Autoimmune Hemolytic Anemia in a Patient with Probable Ataxia Telangiectasia: A Case Report
Soheila
Alyasin
Allergy Research Center
author
Maryam
Khoshkhui
Department of Pediatrics, Division of Immunology and Allergy, Namazi
Hospital, Shiraz, Iran
author
Farhad
Abolnezhadian
Department of Pediatrics, Division of Immunology and Allergy, Namazi
Hospital, Shiraz, Iran
author
text
article
2014
eng
Background: Ataxia telangiectasia (AT) is one of the combined immunodeficiency syndromes with immunologic, neurologic, endocrinologic, hepatic and cutaneous abnormalities. Regarding the fact that autoimmune disorders; such as autoimmune hemolytic anemia (AIHA), are not generally expected in the course of AT, we present a patient with an unusual presentation of these two conditions. Case presentation: An otherwise seemingly normal girl, who had developed limping at the age of 11 months old, referred to Namazi Hospital, Shiraz, Iran, due to pallor and latitude at the age of 3 yrs and was diagnosed with AIHA. After 2 years of therapeutic course she developed ocular telangiectasia and ataxic gate. Conclusion: This case emphasizes the possibility of ataxia telangiectasia coexistence with autoimmune disorders and must be taken into consideration by physicians.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
11
v.
3
no.
2014
217
220
https://iji.sums.ac.ir/article_16782_fa5046b89339f9b2424ab71ab41c4311.pdf