Inflammation is initiated as a protective response by the host, but can often result in systemic pathology. Among cells of the immune system, T lymphocytes play a major role in the inflammatory response. T cell inflammation is characterised histologically by an infiltration of mononuclear cells. Key regulators of this response are a subset of T lymphocytes called T helper (Th) cells. These cells secrete soluble mediators called cytokines, which orchestrate the immune response. The appropriate regulation of Th cell immunity is critical in the control and prevention of diverse disease states. This review will focus on the role of Th cells in the inflammatory process involved in allergic disease, diabetes, infectious disease, rheumatoid arthritis, heart disease, multiple sclerosis and cancer. In the area of autoimmunity, in particular, a basic understanding of Th cells and cytokines has contributed to the development of clinically efficacious biological agents. This review also examines current and novel treatment strategies under investigation at present that regulate Th cell immunity, which may result in better treatments for immune-mediated diseases.
Optophoresis is a non-invasive cell analysis technique that is based on the interaction of live whole cells with optical gradient fields, typically generated by a near-infrared laser. The magnitude of the interaction depends upon the intrinsic physical properties of the cells, such as their refractive index, composition, size, and morphology. Time-of-flight (TOF) optophoresis is an implementation of this technique in a microfluidic environment. It measures cell travel times through a fixed distance with and without irradiation from a laser beam. The magnitude of the optical force from the laser, and therefore the change in transit time introduced by the presence of the infrared laser provides a signature for the cell. By accumulating such measurements for a population of cells (typically 200-300 cells per population), different cell types, drug treatments, or biological states can be compared quantitatively without the need for external labels or markers. An integrated TOF system has been constructed and characterized. The system typically uses square capillaries with 50-100 microm internal diameter and uses a syringe-pump-based flow system that generates initial bulk flow velocities between 200 and 600 microm/sec. Using this TOF technique, we have been able to consistently detect significant differences between normal skin and melanoma cell lines, CCD-1037 and A375, respectively. We have also been able to measure consistent differences in a cell differentiation model (HL60 cell line with DMSO treatment). These early results indicate the potential biological sensitivity of the TOF measurement technique for cellular analysis and cancer diagnostic applications.
Cancer vaccines composed of tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) are currently being clinically evaluated. To enhance the immunogenicity of GM-CSF-secreting tumor cell vaccines, a novel approach expressing GM-CSF as a membrane-bound form (mbGM-CSF) on the tumor cell surface was investigated. The intent was to enhance antigen presentation by increasing interactions between the tumor cell lines in the vaccine and GM-CSF receptor positive antigen presenting cells (APC), notably the patient's Langerhans cells residing within the intradermal injection site. B16.F10 cells engineered to express either membranebound or secreted GM-CSF were compared in the B16.F10 mouse melanoma model. We observed that mbGM-CSF on
Background: Most methods for cellular analysis require labeling with specific antibodies or dyes and are often destructive. We have developed a technology called Optophoresis™, which measures cell physiology based on the cell's motion in a near-infrared optical gradient. This technique does not require labels, is nondestructive, and involves minimal sample processing. Methods: We have used Optophoresis to interrogate nonproductive and productive adenovirus-infected cell lines. Using an adenoviral vector containing green fluorescent protein (GFP) as a secondary assay, we show that viral infection can be monitored with Optophoresis. Results: In HeLa cells, adenovirus infection after 24 h caused a 12% to 17% increase in optophoretic motility of the cells. In 293 cells, adenovirus infection resulted in a
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