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Cell signaling events are orchestrated by dynamic external biochemical cues. By rapidly perturbing cells with dynamic inputs and examining the output from these systems, one could study the structure and dynamic properties of a cellular signaling network. Conventional experimental techniques limit the implementation of these systematic approaches due to the lack of sophistication in manipulating individual cells and the fluid microenvironment around them; existing microfluidic technologies thus far are mainly targeting adherent cells. In this paper we present an automated platform to interrogate suspension cells with dynamic stimuli while simultaneously monitoring cellular responses in a high-throughput manner at single-cell resolution. We demonstrate the use of this platform in an experiment to measure Jurkat T cells in response to distinct dynamic patterns of stimuli; we find cells exhibit highly heterogeneous responses under each stimulation condition. More interestingly, these cells act as low-pass filters, only entrained to the low frequency stimulus signals. We also demonstrate that this platform can be easily programmed to actively generate arbitrary dynamic signals. We envision our platform to be useful in other contexts to study cellular signaling dynamics, which may be difficult using conventional experimental methods. [ABSTRACT FROM AUTHOR]

Abstract: There is a fundamental difference in complexity between signaling initiated by ligands on the surface of one cell binding to receptors on the surface of another cell and ligands in solution binding to these receptors. The fact that two cells must approach each other and form a number of intercellular bonds of different types, all within the restricted geometry of the intercellular contact region, introduces the possibility of complex spatio-temporal dynamics of surface receptors that is not present otherwise. Mathematical modelling of these dynamics is in its early stages. However, useful tools have emerged. The purpose of this paper is to describe some of these mathematical tools, indicating their strengths and shortcomings, and suggest some directions for future theoretical studies. [Copyright &y& Elsevier]

Abstract: In the present paper, the effect of the aqueous extract from aerial parts of Artemisia vestita (AV-ext), a traditional Tibetan medicine, on ear contact sensitivity was examined. AV-ext significantly reduced the ear swelling when administered during the induction phase of picryl-chloride (PCl)-induced ear contact sensitivity in mice. The extract also showed a dose-dependent inhibition on lymphocyte proliferation and IL-2 production in Con A-activated spleen cells. The proliferation inhibition was confirmed in the mixed lymphocytes reaction. Furthermore, the adhesion of the isolated spleen cells from PCl-sensitized mice to type IV collagen was significantly decreased in a dose-dependent manner by AV-ext. Such decrease was also seen in AV-ext-treated Jurkat T cells and the T cells purified from above spleen cells. The purified spleen T cells from PCl-sensitized mice produced more matrix metalloproteinase-9 (MMP-9) than naive T cells, and AV-ext remarkably reduced MMP-9 production both in vivo and in vitro. These results suggest that AV-ext may alleviate contact sensitivity through blocking the activation of T lymphocytes and decreasing their localization to the inflammatory sites via down-regulating the potential of cell adhesion and metalloproteinase production. [Copyright &y& Elsevier]

Interaction of T lymphocytes with other cell types is important for normal T-cell development and function. Recently, a number of adhesion molecules important in T-cell interactions with other cell types have been defined. In this paper we review the role of two adhesion pathways, CD2/LFA-3 and LFA-1/ICAM-1, in T-cell interactions with epithelial cells of the thymus and skin. While thymic epithelium-T-cell interactions were mediated by both the LFA-1/ICAM-1 pathway and the CD2/LFA-3 pathway, epidermal-T-cell interactions were mediated primarily by the LFA-1/ICAM-1 pathway. Although ICAM-1 was not expressed in vivo on epidermal keratinocytes in normal skin, ICAM-1 was expressed by epidermal keratinocytes at the site of T-cell infiltration in inflammatory dermatitis. ICAM-1 was expressed in vivo on thymic epithelium. Both LFA-3 and ICAM-1 were expressed on epithelial cells of thymus and skin early on in fetal ontogeny. These antigen-independent adhesion molecules play an important role in the cell-cell interactions associated with T-cell differentiation and function. [ABSTRACT FROM AUTHOR]

The article discusses a research paper on expression of melanoma cell adhesion molecule (MCAM) on pathogenic T cells that enter the central nervous system (CNS). It references a study by Catherine Larochelle et al., published in an issue of "Brain". The study shows that MCAM is expressed by a subset of inflammatory T cells and endothelial cells and facilitates T-cell entry into the CNS during multiple sclerosis.