T-Cell Artificial Focal Triggering Tools: Linking Surface Interactions with Cell Response

T-cell activation is a key event in the immune system, involving the interaction of several receptor ligand pairs in a complex intercellular contact that forms between T-cell and antigen-presenting cells. Molecular components implicated in contact formation have been identified, but the mechanism of activation and the link between molecular interactions and cell response remain poorly understood due to the complexity and dynamics exhibited by whole cell-cell conjugates. Here we demonstrate that simplified model colloids grafted so as to target appropriate cell receptors can be efficiently used to explore the relationship of receptor engagement to the T-cell response. Using immortalized Jurkat T cells, we monitored both binding and activation events, as seen by changes in the intracellular calcium concentration. Our experimental strategy used flow cytometry analysis to follow the short time scale cell response in populations of thousands of cells. We targeted both T-cell receptor CD3 (TCR/CD3) and leukocyte-function-associated antigen (LFA-1) alone or in combination. We showed that specific engagement of TCR/CD3 with a single particle induced a transient calcium signal, confirming previous results and validating our approach. By decreasing anti-CD3 particle density, we showed that contact nucleation was the most crucial and determining step in the cell-particle interaction under dynamic conditions, due to shear stress produced by hydrodynamic flow. Introduction of LFA-1 adhesion molecule ligands at the surface of the particle overcame this limitation and elucidated the low TCR/CD3 ligand density regime. Despite their simplicity, model colloids induced relevant biological responses which consistently echoed whole cell behavior. We thus concluded that this biophysical approach provides useful tools for investigating initial events in T-cell activation, and should enable the design of intelligent artificial systems for adoptive immunotherapy

Teacher–researcher partnership in the translation and implementing of PALS (Peer-Assisted Learning Strategies): an international perspective

Peer-Assisted Learning Strategies (PALS) is a class-wide structured supplementary paired reading programme to support learners with their reading (Fuchs et al., 1997). What remains at the core of implementing PALS in any given location is the co-creation with teachers to ensure PALS fits with that educational context. This paper discusses the involvement of teachers as co-creators in the process of adapting PALS in England, United Arab Emirates (UAE), Taiwan and Iceland. The aim is to demonstrate the importance of careful adaptation when implementing a programme adopted from another country. Each adaption used a different methodological approach to co-creation. For example, in England, field notes, informal conversations and interviews were utilised for co-creation. In Iceland, preschool and elementary teachers were instrumental in translating and adapting the PALS materials to the Icelandic context. From each adaption, the teachers supported the development of a literacy programme that was suitable for classroom use. In England, teachers' involvement resulted in the removal of the motivational point system. For the UAE context, PALS began in English to support second language learning, but the instructional routines were a good ‘fit’ for the school culture and were developed in Arabic. For the Taiwan context, PALS provided an empirical basis for a model of differentiated instruction to enhance the reading literacy of Chinese-speaking elementary students. In Iceland, teachers trained other teachers in PALS as a research-based and efficient approach to meeting diverse learning needs of students, especially those with Icelandic as an additional language. Careful adaptation, piloting and the involvement of key stakeholders is important for the successful implementation of a reading programme

The kinase p38 alpha serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression

p38 mitogen-activated protein kinase (MAPK) mediates cellular responses to injurious stress and immune signaling. Among the multiple p38 isoforms, p38α is the most widely expressed in adult tissues and can be targeted by various pharmacological inhibitors. Here we investigated how p38α activation is linked to cell type-specific outputs using mouse models of cutaneous inflammation. We showed that both myeloid and epithelial p38α can signal to evoke inflammatory responses, yet the mode of skin irritation determines the cell type in which p38α serves the function. In addition, myeloid p38α induces self-limitation of acute inflammation via activation of MSK-dependent anti-inflammatory gene expression. These suggest a dual role of p38α in regulation of inflammation, and reveal a mixed potential for its inhibition as a therapeutic strategy