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T cell growth factor [keywords]
- Murine Granulocyte-Macrophage Colony-Stimulating Factor Expressed from a Bicistronic Simian Immunodeficiency Virus-Based Integrase-Defective Lentiviral Vector Does Not Enhance T-Cell Responses in Mice. [JOURNAL ARTICLE]
- Viral Immunol 2014 Oct 24.
Abstract As a prelude to immunization studies in nonhuman primates, we compared in mice the immunogenicity of a simian immunodeficiency virus (SIV)-based integrase (IN)-defective lentiviral vector (IDLV) encoding the model antigen-enhanced green fluorescence protein (eGFP) in the presence or absence of the murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) expressed from an internal ribosomal entry site (IRES) sequence. BALB/c mice were immunized once intramuscularly with IDLV expressing eGFP alone or eGFP and mGM-CSF and immune responses were evaluated up to 90 days from the single intramuscular immunization. Results indicated that the mGM-CSF was unable to improve the magnitude and quality of the immune response against the eGFP transgene in the context of the SIV-based IDLV, as evaluated by enzyme-linked immunosorbent spot (ELISPOT) assays for interferon-γ (IFN-γ) and by intracellular cytokine staining for IFN-γ, interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-α). These findings suggest that for vaccination purposes, the presence of mGM-CSF expressed after the IRES in a SIV-based IDLV system does not favor the improvement of the immunological response against the transgene of interest. Further studies should investigate whether the selection of a different cytokine gene might improve the immune response against the transgene.
- High-dose IL-2 for metastatic renal cell carcinoma: can the first antitumor immunotherapy be reinvented? [JOURNAL ARTICLE]
- Immunotherapy 2014 Sep; 6(9):955-958.
- [Thalidomide in combination with interferon and interleukin 2 in the induction therapy for relapsed refractory acute myeloid leukemia: two case report and literature review]. [Journal Article]
- Zhonghua Xue Ye Xue Za Zhi 2014 Oct 14; 35(10):954-6.
- Interleukin-2-Inducible T-Cell Kinase (ITK) Deficiency - Clinical and Molecular Aspects. [JOURNAL ARTICLE]
- J Clin Immunol 2014 Oct 24.
In patients with underlying immunodeficiency, Epstein-Barr virus (EBV) may lead to severe immune dysregulation manifesting as fatal mononucleosis, lymphoma, lymphoproliferative disease (LPD), lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis (HLH) and dysgammaglobulinemia. Several newly discovered primary immunodeficiencies (STK4, CD27, MAGT1, CORO1A) have been described in recent years; our group and collaborators were able to reveal the pathogenicity of mutations in the Interleukin-2-inducible T-cell Kinase (ITK) in a cohort of nine patients with most patients presenting with massive EBV B-cell lymphoproliferation. This review summarizes the clinical and immunological findings in these patients. Moreover, we describe the functional consequences of the mutations and draw comparisons with the extensively investigated function of ITK in vitro and in the murine model.
- [Construction and In Vitro Study of Eukaryotic Expression Vector Carrying GITRL and IL-21 Gene]. [English Abstract, Journal Article]
- Zhongguo Shi Yan Xue Ye Xue Za Zhi 2014 Sep; 22(5):1295-300.
The aim of this study was to construct the eukaryotic expression vector carrying glucocorticoid-induced tumor necrosis factor receptor ligand (GITRL) and interleukin-21 (IL-21) gene for transfection into chronic myeloid leukemia (CML) dervied dendritic cell (DC), so as to provide an effective platform for exploring the function of target gene in CML. The recombinant eukaryotic expression vector was transfected to the purified DC by Liposome-mediated method, the interleukin-2 (IL-2) and Interferon-γ (IFN-γ) expression of transfected DC were analyzed by ELISA. Further, the transfected DC with purified NK were mixed and cultured to be DC-CIK, the lactate dehydrogenase release assay was performed to measure the killing activity of DC-CIK. The results indicated that the sequence of cloned target gene was same as that in GenBank. The size of endonuclease products by restriction enzyme were same as the predict one. The concentration of Interleukin-2 (IL-2) and interferon-γ (IFN-γ) in transfected DC all increased. The NK kill activity became stronger while induced by transfected DC. It is concluded that DC transfected by IL-21 and GITRL gene has the ability of self-activation, up-regulate cytokine secretion. Further, the results would be help to provide the theoretical evidence of advanced immunotherapy for treatment of CML patients who showed no reaction to tyrosine kinase inhibitor.
- The Effects of Cold Exposure on Leukocytes, Hormones and Cytokines during Acute Exercise in Humans. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e110774.
The purpose of the study was to examine the effects of exercise on total leukocyte count and subsets, as well as hormone and cytokine responses in a thermoneutral and cold environment, with and without an individualized pre-cooling protocol inducing low-intensity shivering. Nine healthy young men participated in six experimental trials wearing shorts and t-shirts. Participants exercised for 60 min on a treadmill at low (LOW: 50% of peak VO2) and moderate (MOD: 70% VO2peak) exercise intensities in a climatic chamber set at 22°C (NT), and in 0°C (COLD) with and without a pre-exercise low-intensity shivering protocol (SHIV). Core and skin temperature, heart rate and oxygen consumption were collected continuously. Blood samples were collected before and at the end of exercise to assess endocrine and immunological changes. Core temperature in NT was greater than COLD and SHIV by 0.4±0.2°C whereas skin temperature in NT was also greater than COLD and SHIV by 8.5±1.4°C and 9.3±2.5°C respectively in MOD. Total testosterone, adenocorticotropin and cortisol were greater in NT vs. COLD and SHIV in MOD. Norepinephrine was greater in NT vs. other conditions across intensities. Interleukin-2, IL-5, IL-7, IL-10, IL-17, IFN-γ, Rantes, Eotaxin, IP-10, MIP-1β, MCP-1, VEGF, PDGF, and G-CSF were elevated in NT vs. COLD and/or SHIV. Furthermore, IFN-γ, MIP-1β, MCP-1, IL-10, VEGF, and PDGF demonstrate greater concentrations in SHIV vs. COLD, mainly in the MOD condition. This study demonstrated that exercising in the cold can diminish the exercise-induced systemic inflammatory response seen in a thermoneutral environment. Nonetheless, prolonged cooling inducing shivering thermogenesis prior to exercise, may induce an immuno-stimulatory response following moderate intensity exercise. Performing exercise in cold environments can be a useful strategy in partially inhibiting the acute systemic inflammatory response from exercise but oppositely, additional body cooling may reverse this benefit.
- Cellular microRNAs up-regulate transcription via interaction with promoter TATA-box motifs. [JOURNAL ARTICLE]
- RNA 2014 Oct 21.
The TATA box represents one of the most prevalent core promoters where the pre-initiation complexes (PICs) for gene transcription are assembled. This assembly is crucial for transcription initiation and well regulated. Here we show that some cellular microRNAs (miRNAs) are associated with RNA polymerase II (Pol II) and TATA box-binding protein (TBP) in human peripheral blood mononuclear cells (PBMCs). Among them, let-7i sequence specifically binds to the TATA-box motif of interleukin-2 (IL-2) gene and elevates IL-2 mRNA and protein production in CD4(+) T-lymphocytes in vitro and in vivo. Through direct interaction with the TATA-box motif, let-7i facilitates the PIC assembly and transcription initiation of IL-2 promoter. Several other cellular miRNAs, such as mir-138, mir-92a or mir-181d, also enhance the promoter activities via binding to the TATA-box motifs of insulin, calcitonin or c-myc, respectively. In agreement with the finding that an HIV-1-encoded miRNA could enhance viral replication through targeting the viral promoter TATA-box motif, our data demonstrate that the interaction with core transcription machinery is a novel mechanism for miRNAs to regulate gene expression.
- Near-Infrared Imaging of Adoptive Immune Cell Therapy in Breast Cancer Model Using Cell Membrane Labeling. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e109162.
The overall objective of this study is to non-invasively image and assess tumor targeting and retention of directly labeled T-lymphocytes following their adoptive transfer in mice. T-lymphocytes obtained from draining lymph nodes of 4T1 (murine breast cancer cell) sensitized BALB/C mice were activated in-vitro with Bryostatin/Ionomycin for 18 hours, and were grown in the presence of Interleukin-2 for 6 days. T-lymphocytes were then directly labeled with 1,1-dioctadecyltetramethyl indotricarbocyanine Iodide (DiR), a lipophilic near infrared fluorescent dye that labels the cell membrane. Assays for viability, proliferation, and function of labeled T-lymphocytes showed that they were unaffected by DiR labeling. The DiR labeled cells were injected via tail vein in mice bearing 4T1 tumors in the flank. In some cases labeled 4T1 specific T-lymphocytes were injected a week before 4T1 tumor cell implantation. Multi-spectral in vivo fluorescence imaging was done to subtract the autofluorescence and isolate the near infrared signal carried by the T-lymphocytes. In recipient mice with established 4T1 tumors, labeled 4T1 specific T-lymphocytes showed marked tumor retention, which peaked 6 days post infusion and persisted at the tumor site for up to 3 weeks. When 4T1 tumor cells were implanted 1-week post-infusion of labeled T-lymphocytes, T-lymphocytes responded to the immunologic challenge and accumulated at the site of 4T1 cell implantation within two hours and the signal persisted for 2 more weeks. Tumor accumulation of labeled 4T1 specific T-lymphocytes was absent in mice bearing Meth A sarcoma tumors. When lysate of 4T1 specific labeled T-lymphocytes was injected into 4T1 tumor bearing mice the near infrared signal was not detected at the tumor site. In conclusion, our validated results confirm that the near infrared signal detected at the tumor site represents the DiR labeled 4T1 specific viable T-lymphocytes and their response to immunologic challenge can be imaged in vivo.
- Functionally distinct subsets of CD4+ regulatory T cells in patients with laryngeal squamous cell carcinoma are indicative of immune deregulation and disease progression. [JOURNAL ARTICLE]
- Oncol Rep 2014 Oct 20.
CD4+ regulatory T cells (Tregs) mediate immune tolerance in laryngeal squamous cell carcinoma (LSCC). However, Tregs are functionally heterogeneous. Recently, we reported that three distinct Treg subsets (resting Tregs, activated Tregs and cytokine-secreting CD45RA-Foxp3lowCD4+ T cells) vary in the peripheral circulation of patients with head and neck squamous cell carcinoma (HNSCC); however, the potential implication of these Treg subsets in LSCC immunity is unclear. Here, we report that activated Tregs and cytokine‑secreting CD45RA-Foxp3lowCD4+ T cells were increased in LSCC patients compared with healthy donors (HD) (p<0.001, p<0.001), whereas resting Tregs were decreased (p<0.001). Activated Tregs inhibited the proliferation of CD4+CD25- T cells (p<0.001) and secreted lower levels of interleukin-2 (p<0.001), interferon-γ (p<0.001) and tumor necrosis factor-α (p<0.001) compared with the cytokine-secreting CD45RA-Foxp3lowCD4+ T cells. Importantly, activated Treg prevalence was correlated with tumor stage (p=0.001) and nodal status (p=0.007). The prevalence of naïve CD4+ (p<0.001), naïve CD8+ (p=0.002), and Th1 T-cell subsets (p<0.001, p<0.001) was decreased in the LSCC patients. In conclusion, our findings showed that activated Tregs with suppressive activity are a distinct subset of Tregs in LSCC, and correlate with disease progression. Several immune system abnormalities in LSCC patients are represented by expansion of functionally activated Tregs, both in the circulation and tumor microenvironment along with decreased frequencies of naïve T-cell populations and Th1-cell populations.
- β(1-3)(1-6)-D-glucans modulate immune status in pigs: potential importance for efficiency of commercial farming. [Journal Article]
- Ann Transl Med 2014 Feb; 2(2):16.
In face of the challenge of the emergent diseases and the current efforts of the governments to create conditions to ban growth-promoting antibiotics and to improve efficiency of the commercial farming, new opportunities are created for natural, highly effective and cost affordable immunomodulators; able to induce and enhance resistance against diseases and to reduce farming-related stress. Supplementation of animal feed with β(1-3)(1-6)-D-glucans has been repeatedly shown to modulate the immune system ant to influence growth characteristics of farmed animals.In our study we focused on evaluation of effects of an insoluble, fungi-derived β(1-3)(1-6)-D-glucan as dietary supplement in piglets. We measured the growth, phagocytosis of peripheral blood cells and interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α) production after feeding with 15 mg of glucan/kg/day.Following supplementation, β(1-3)(1-6)-D-glucan has been shown to stimulate growth, phagocytic activity, and IL-2 production. In addition, it significantly lowered the cortisol and TNF-α levels after lipopolysaccharide (LPS) challenge.