Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
T cell growth factor [keywords]
- 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.
- Southwest Oncology Group S0008: A Phase III Trial of High-Dose Interferon Alfa-2b Versus Cisplatin, Vinblastine, and Dacarbazine DTIC, Plus Interleukin-2 and Interferon in Patients With High-Risk Melanoma-An Intergroup Study of Cancer and Leukemia Group B, Children's Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. [JOURNAL ARTICLE]
- J Clin Oncol 2014 Oct 20.
High-dose interferon (IFN) for 1 year (HDI) is the US Food and Drug Administration-approved adjuvant therapy for patients with high-risk melanoma. Efforts to modify IFN dose and schedule have not improved efficacy. We sought to determine whether a shorter course of biochemotherapy would be more effective.S0008 (S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma) was an Intergroup phase III trial that enrolled high-risk patients (stage IIIA-N2a through IIIC-N3), randomly assigning them to receive either HDI or biochemotherapy consisting of dacarbazine DTIC, cisplatin, vinblastine, interleukin-2, IFN alfa-2b (IFN-α-2b) and granulocyte colony-stimulating factor given every 21 days for three cycles. Coprimary end points were relapse-free survival (RFS) and overall survival (OS).In all, 432 patients were enrolled. Grade 3 and 4 adverse events occurred in 57% and 7% of HDI patients and 36% and 40% of biochemotherapy patients, respectively. At a median follow-up of 7.2 years, biochemotherapy improved RFS (hazard ratio [HR], 0.75; 95% CI, 0.58 to 0.97;P = .015), with a median RFS of 4.0 years (95% CI, 1.9 years to not reached [NR]) versus 1.9 years for HDI (95% CI, 1.2 to 2.8 years) and a 5-year RFS of 48% versus 39%. Median OS was not different (HR, 0.98; 95% CI, 0.74 to 1.31;P = .55), with a median OS of 9.9 years (95% CI, 4.62 years to NR) for biochemotherapy versus 6.7 years (95% CI, 4.5 years to NR) for HDI and a 5-year OS of 56% for both arms.Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in RFS but no difference in OS and more toxicity compared with HDI.
- Melanoma of the oral cavity: pathogenesis, dermoscopy, clinical features, staging and management. [Journal Article]
- J Dermatol Case Rep 2014 Sep 30; 8(3):60-6.
Primary mucosal melanoma of the oral cavity is an exceedingly rare neoplasm which is estimated to comprise 1-2% of all oral malignancies. In contrast to cutaneous melanomas, the risk factors and pathogenesis are poorly understood. The predominate localization of primary oral melanoma is hard palate and maxillary alveolus. Dermoscopy may be utilized as an adjunctive tool in the clinical differential diagnosis of oral mucosal melanoma whenever the lesion is accessible with a dermoscope. Surgery is the mainstay of treatment, but it may be challenging depending on the location of the tumor within the oral cavity and its size. Adjuvant therapy with dacarbazine, platinum analogs, nitrosoureas and interleukin-2 have been utilized with low response rates. Imatinib may be effective for patients with with c-Kit gene mutations. Sunitinib and dasatinib have been reported effective in selected cases. Vemurafenib and dabrafenib are targeted agents for patients with BRAF mutation-positive melanoma. Ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 antibody and pembrolizumab, a monoclonal antibody targeting programmed death 1 receptor may be a feasible treatment option in patients with metastatic mucosal melanoma.
- Interleukin-5 producing group 2 innate lymphoid cells (ILC2) control eosinophilia induced by interleukin-2 therapy. [JOURNAL ARTICLE]
- Blood 2014 Oct 16.
Interleukin (IL)-2 promotes regulatory T cell development and function and treatment with IL-2 is being tested as therapy for some autoimmune diseases. However, patients receiving IL-2 treatment also experience eosinophilia due to an unknown mechanism. Here we show that patients receiving low dose IL-2 have elevated levels of serum IL-5 and this correlates with their degree of eosinophilia. In mice, low dose IL-2-anti IL-2 antibody complexes drove group 2 innate lymphoid cells (ILC2) to produce IL-5 and proliferate. Using genetic approaches in mice, we demonstrate that activation of ILC2 was responsible for the eosinophilia observed with IL-2 therapy. These observations reveal a novel cellular network that is activated during IL-2 treatment. A better understanding of the cross-talk between these cell populations may lead to more effective targeting of IL-2 to treat autoimmune disease.
- Low-Dose Interleukin-2 Therapy: A Driver of an Imbalance between Immune Tolerance and Autoimmunity. [REVIEW]
- Int J Mol Sci 2014; 15(10):18574-18592.
For many years, the role of interleukin-2 (IL-2) in autoimmune responses was established as a cytokine possessing strong pro-inflammatory activity. Studies of the past few years have changed our knowledge on IL-2 in autoimmune chronic inflammation, suggesting its protective role, when administered at low-doses. The disrupted balance between regulatory and effector T cells (Tregs and Teffs, respectively) is a characteristic of autoimmune diseases, and is dependent on homeostatic cytokines, including IL-2. Actually, inherent defects in the IL-2 signaling pathway and/or levels leading to Treg compromised function and numbers as well as Th17 expansion have been attributed to autoimmune disorders. In this review, we discuss the role of IL-2 in the pathogenesis of autoimmune diseases. In particular, we highlight the impact of the dysregulated IL-2 pathway on disruption of the Treg/Th17 balance, reversal of which appears to be a possible mechanism of the low-dose IL-2 treatment. The negative effects of IL-2 on the differentiation of follicular helper T cells (Tfh) and pathogenic Th17 cells, both of which contribute to autoimmunity, is emphasized in the paper as well. We also compare the current IL-2-based therapies of animal and human subjects with immune-mediated diseases aimed at boosting the Treg population, which is the most IL-2-dependent cell subset desirable for sufficient control of autoimmunity. New perspectives of therapeutic approaches focused on selective delivery of IL-2 to inflamed tissues, thus allowing local activity of IL-2 to be combined with its reduced systemic and pleiotropic toxicity, are also proposed in this paper.
- T cells promote the regeneration of neural precursor cells in the hippocampus of Alzheimer's disease mice. [Journal Article]
- Neural Regen Res 2014 Aug 15; 9(16):1541-7.
Alzheimer's disease is closely associated with disorders of neurogenesis in the brain, and growing evidence supports the involvement of immunological mechanisms in the development of the disease. However, at present, the role of T cells in neuronal regeneration in the brain is unknown. We injected amyloid-beta 1-42 peptide into the hippocampus of six BALB/c wild-type mice and six BALB/c-nude mice with T-cell immunodeficiency to establish an animal model of Alzheimer's disease. A further six mice of each genotype were injected with same volume of normal saline. Immunohistochemistry revealed that the number of regenerated neural progenitor cells in the hippocampus of BALB/c wild-type mice was significantly higher than that in BALB/c-nude mice. Quantitative fluorescence PCR assay showed that the expression levels of peripheral T cell-associated cytokines (interleukin-2, interferon-γ) and hippocampal microglia-related cytokines (interleukin-1β, tumor necrosis factor-α) correlated with the number of regenerated neural progenitor cells in the hippocampus. These results indicate that T cells promote hippocampal neurogenesis in Alzheimer's disease and T-cell immunodeficiency restricts neuronal regeneration in the hippocampus. The mechanism underlying the promotion of neuronal regeneration by T cells is mediated by an increased expression of peripheral T cells and central microglial cytokines in Alzheimer's disease mice. Our findings provide an experimental basis for understanding the role of T cells in Alzheimer's disease.
- Immunomodulatory Effects of Newcastle Disease Virus AF2240 Strain on Human Peripheral Blood Mononuclear Cells. [Journal Article]
- Int J Med Sci 2014; 11(12):1240-7.
Immunotherapy has raised the attention of many scientists because it hold promise to be an attractive therapeutic strategy to treat a number of disorders. In this study, the immunomodulatory effects of low titers of Newcastle disease virus (NDV) AF2240 on human peripheral blood mononuclear cells (PBMC) were analyzed. We evaluated cytokine secretion and PBMC activation by cell proliferation assay, immunophenotyping and enzyme linked immunosorbent assay. The proliferation of the human PBMC was measured to be 28.5% and 36.5% upon treatment with 8 hemaglutinin unit (HAU) and 2 HAU of NDV respectively. Interestingly, the percentage of cells with activating markers CD16 and CD56 were increased significantly. Furthermore, the intracellular perforin and granzyme levels were also increased upon virus infection. Human PBMC treated with NDV titer 8 HAU was found to stimulate the highest level of cytokine production including interferon-γ, interleukin-2 and interleukin-12. The release of these proteins contributes to the antitumor effect of PBMC against MCF-7 breast cancer cells. Based on the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay, activated human PBMC showed high cytolytic efficiency towards human breast tumor cells. In summary, NDV was able to stimulate PBMC proliferation, cytokine secretion and cytolytic activity.
- Sarcoidosis of female reproductive organs in a postmenopausal woman: a case report and review of the literature: is there a potential for hormone therapy? [JOURNAL ARTICLE]
- Menopause 2014 Oct 13.
Sarcoidosis is a multisystem inflammatory disorder of unknown cause that affects multiple organs. To date, only isolated cases of extrapulmonary sarcoidosis of the female reproductive tract, which rarely affects postmenopausal women, have been reported.We describe the case of a postmenopausal woman with sarcoidosis of multiple structures of the genital tract accompanied by pulmonary involvement. A review of the literature was performed to examine the role of sex hormones in the pathogenesis of sarcoidosis.We describe the case of a 60-year-old white, nulliparous, nulligravid postmenopausal woman with sarcoidosis of the cervix, uterus, mesosalpinx, and right ovary, accompanied by pulmonary involvement. The diagnosis was based on the identification of noncaseating granulomas in reproductive tract organs. Although imaging methods (high-resolution CT and chest x-ray) and pulmonary function tests did not reveal any abnormality, lung involvement was confirmed histologically by transbronchial biopsy. Treatment with steroids was successful and led to normalization of serum biomarker (serum angiotensin-converting enzyme, soluble interleukin-2 receptor, and neopterin) levels.This particular case and a brief literature review of female genital tract sarcoidosis in postmenopausal women suggest the role of sex hormones in the pathogenesis of sarcoidosis. Hormone therapy may be a prospective therapeutic alternative to corticosteroids in postmenopausal women.