The role of γδ T cells in immunotherapy has gained specific importance in the recent years because of their prominent function involving directly or indirectly in the rehabilitation of the diseases. γδ T cells represent a minor population of T cells that express a distinct T cell receptor (TCR) composed of γδ chains instead of αβ chains. Unlike αβ T cells, γδ T cells display a restricted TCR repertoire and recognize mostly unknown non-peptide antigens. γδ T cells act as a link between innate and adaptive immunity, because they lack precise major histocompatibility complex (MHC) restriction and seize the ability to recognize ligands that are generated during affliction. Skin epidermal γδ T cells recognize antigen expressed by damaged or stressed keratinocytes and play an indispensable role in tissue homeostasis and repair through secretion of distinct growth factors. γδ T cell based immunotherapy strategies possess great prominence in the treatment because of the property of their MHC-independent cytotoxicity, copious amount of cytokine release, and a immediate response in infections. Understanding the role of γδ T cells in pathogenic infections, wound healing, autoimmune diseases, and cancer might provide knowledge for the successful treatment of these diseases using γδ T cell based immunotherapy. Enhancing the human Vγ9Vδ2 T cells functions by administration of aminobisphosphonates like zoledronate, pamidronate, and bromohydrin pyrophosphate along with cytokines and monoclonal antibodies shows a hopeful approach for treatment of tumors and infections. The current review summarizes the role of γδ T cells in various human diseases and immunotherapeutic approaches using γδ T cells.
Ovarian cancer is the most lethal malignancy of the female reproductive system and the fifth leading cause of cancer death in women. In the year 2012 alone, United States had 22,280 new ovarian cancer cases and 15,500 deaths were reported. About 7%-10% of ovarian cancers result from an inherited tendency to develop the disease. Ovarian cancer has the ability to escape the immune system because of its pathological interactions between cancer cells and host immune cells in the tumor microenvironment create an immunosuppressive network that promotes tumor growth, protects the tumor from immune system. The levels of immune suppressive elements like regulatory T cells, plasmacytoid dendritic cells and cytokines such as IL-10, IL-6, TNF-α, and TGF-β are elevated in the tumor microenvironment. Vascular endothelial growth factor is known to have an immune suppressing role besides its angiogenic role in the tumor microenvironment. Ovarian cancer is associated with high mortality partly due to difficulties in early diagnosis and development of metastases. These problems may overcome by developing accurate mouse models that should mimic the complexity of human ovarian cancer. Such animal models are better suited to understand pathophysiology, metastases, and also for preclinical testing of targeted molecular therapeutics. Immunotherapy is an area of active investigation and off late many clinical trials is ongoing to prevent disease progression. The main aim of dendritic cells vaccination is to stimulate tumor specific effector T cells that can reduce tumor size and induce immunological memory to prevent tumor relapse.
OBJECTIVES:Although titanium dioxide (TiO2) nanostructural materials have been widely used in Biology and Medicine, very little is known about immunomodulation mechanism of these materials. Objectives of this study are to investigate in vitro immunomodulatory effects of TiO2. Immunosuppressant may lower immune responses and are helpful for the treatment of graft versus host diseases and autoimmune disorders.MATERIALS AND METHODS:In this study, we used H2Ti3O7 titanium dioxide nanotubes (TNT) nanotubes along with commercial TiO2 nanoparticles (TNP) and TiO2 fine particles (TFP). We investigated the in vitro immunomodulatory effects of TNP, TNT, and TFP using mixed lymphocyte reaction (MLR). Suppression was studied by 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Cytokine profile was measured by enzyme-linked immunosorbent assay (ELISA).RESULTS AND CONCLUSIONS:The results from this study illustrated that the TiO2 nanostructural materials strongly suppressed splenocytes proliferation in MLR. For TNP and TNT, at 50 μg/ml suppression of 20%–25% and 30%–35%, respectively, and for TFP at 100 μg/ml suppression was 25%–30% was observed. Suppression of splenocytes proliferation in the presence of TNP, TNT, and TFP demonstrated that these nanostructural materials probably block T-cell-mediated responses in vitro. Our ELISA results confirmed that significantly lower levels of Th1 type cytokines (interleukin-2, interferon-γ) in the 48 h MLR culture supernatants. Our data suggest that TiO2 nanostructural materials suppress splenocytes proliferation by suppressing Th1 cytokines.
Administration of Ti–O based nanomaterials ameliorated the clinical severity of experimental autoimmune encephalomyelitis and collagen induced arthritis, thus provide novel therapeutic approach for multiple sclerosis and rheumatoid arthritis.
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