Hossein Rezvan; Ali Khodadadi; Selman Ali
Abstract
Background: Leishmania is a pathogenic parasite which infects mononuclear cells in vertebrate hosts. Different strategies have been taken to develop immunity against Leishmania . DCs loaded with immunogenic antigen have resulted in different levels of Th1-type immune response and cytotoxic T lymphocytes ...
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Background: Leishmania is a pathogenic parasite which infects mononuclear cells in vertebrate hosts. Different strategies have been taken to develop immunity against Leishmania . DCs loaded with immunogenic antigen have resulted in different levels of Th1-type immune response and cytotoxic T lymphocytes (CTL) activity. Objective: To evaluate the potency of DCs primed with soluble Leishmania mexicana antigens (SLA) in developing CTL activity. Methods: DCs were loaded with SLA and injected to Balb/c mice. After two weeks the mice were sacrificed and their splenocytes were used as effector cells in a standard 4-hour cytotoxicity assay against DCs transfected with pcDNA3 containing L. mexicana gp63 gene. Results: Immunization of Balb/c mice with DCs loaded with SLA resulted in high levels of CTL activity against DCs transfected with pcDNA3 containing L. mexicana gp63 gene. Conclusions: The results indicate a high potency for DCs primed with Leishmania antigens in inducing CTL activity, which can be used for developing an immunogenic vaccine against Leishmania.
Shirin Farjadian; Marzie Norouzian; Vahid Younesi; Azin Ebrahimpour; Ramin Lotfi
Abstract
Background: Although there is convincing data in support of the effectiveness of hyperthermia in tumor therapy, the molecular mechanisms underlying the clinical effects of hyperthermia are still poorly understood. Objective: To investigate natural killer (NK) cell cytotoxicity against heat-treated SW-872 ...
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Background: Although there is convincing data in support of the effectiveness of hyperthermia in tumor therapy, the molecular mechanisms underlying the clinical effects of hyperthermia are still poorly understood. Objective: To investigate natural killer (NK) cell cytotoxicity against heat-treated SW-872 and HeLa tumor cell lines. Methods: NKG2D ligands and HLA class I transcription were examined using quantitative real-time PCR in treated tumor cell lines at 0, 2, 4, 6 and 12 h following thermal treatment at 39C and 42C for 1 h. The expression of MICA/B, ULBP1 and ULBP2 were also determined by flow cytometry. NK92-MI cytotoxic activity against heat-treated target cell lines was assessed by LDH release as well as annexin-V and 7-AAD assays. Results: Our results showed that heat treatment at 39C improved the cytolytic activity of NK cells against SW-872 cells without increasing NKG2D ligand concentration or decreasing HLA class I levels. Conclusion: The observed increase in the cytotoxicity of NK cells against SW-872 cells after hyperthermia does not coincide with changes in MICA/B, ULBP1 and ULBP2 ligands of NKG2, however, the expression of other ligands in target cells may have made the cells susceptible to the cytotoxic effect of NK cells.
Mohammad Jafar Mahmoudi; Maryam Mahmoudi; Fereydoon Siassi; Fazel Shokri; Mohammad Reza Eshraghian; Amir Hassan Zamani; Reza Chahardoli; Mona Hedayat; Jalal Khoshnoodi; Hashem Nayeri; Nima Rezaei; Ali-Akbar Saboor-Yaraghi
Abstract
Background: Atherosclerosis, a chronic inflammatory disease of the vessel wall is characterized by local and systemic immune responses to a variety of antigens. Oxidized low-density lipoprotein (oxLDL) is considered as an important determining factor in the pathogenesis of atherosclerosis. Objective: ...
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Background: Atherosclerosis, a chronic inflammatory disease of the vessel wall is characterized by local and systemic immune responses to a variety of antigens. Oxidized low-density lipoprotein (oxLDL) is considered as an important determining factor in the pathogenesis of atherosclerosis. Objective: The purpose of this study was to investigate the degree of peripheral blood mononuclear cells (PBMC) vulnerability to in vitro oxLDL-induced cytotoxicity from atherosclerotic patients in comparison to healthy individuals. Methods: Thirty patients with atherosclerotic lesions, confirmed by angiography, and 30 matched healthy individuals were investigated. PBMC was prepared from individuals' blood samples which were further stimulated with low dose (1 μg/mL) and high dose (50 μg/mL) of extensively oxidized LDL. MTT assay was utilized to measure cell viability and proliferation. Stimulation index (SI) was calculated as mean ratio of optical density (OD) of the stimulated cells divided by OD of untreated cells. Results: Low dose oxLDL treatment caused no significant proliferative or cytotoxic effect in the control group; however, similar treatment caused significant cytotoxic effect in the patient group compared to the controls (p=0.026). High dose oxLDL treatment induced more significant cytotoxicity in the patient compared to the control group (p=0.006). Comparison of the SI between the two groups of patients and controls showed significantly lower index by either the low (p=0.03) or the high dose (p<0.001) oxLDL in the patients compared to the controls. Conclusions: PBMC from patients with atherosclerosis showed increased susceptibility to oxLDL-induced cytotoxicity. Our results imply that prolonged exposure to elevated levels of circulating oxLDL could weaken the cellular defense mechanisms by progressive depletion of the pool of antiapoptotic proteins, rendering the cells more vulnerable to oxLDL-induced cell death.
