Trinitrophenol Reactive T-Cell Hybridomas Recognize Antigens That Require Antigen Processing

Protein antigens must be taken up, processed, and displayed on the surface of antigen-presenting cells in association with major histocompatibility complex molecules before they can be recognized by T cells. Whether recognition of the haptens used to study allergic contact hypersensitivity in murine models similarly requires processing has not been determined. We analyzed whether presentation of trinitrophenol to trinitrophenol reactive T-cell hybridomas requires antigen processing by studying the effects of inhibitors of antigen processing and presentation on tile ability of a syngeneic B-cell tumor (A20) to present trinitrophenol to a series of interleukin-2 producing, trinitrophenol specific, major histocompatibility complex class II-restricted T-cell hybridomas.The ability of trinitrophenol modified A20 cells to stimulate the hybridomas was completely inhibited by rnonoclonal, anti-trinitrophenol, or anti-Ia antibodies and was significantly reduced by paraformaldehyde fixation immediately after trinitrophenol modification. Trinitrophenol-modified A20 cultured at 37°C for 2h prior to fixation was significantly more effective at stimulating the hybridomas than trinitrophenol-modified A20 to present trinitrophenol was inhibited by chloroquine. Paraformaldehyde fixation and chloroquine treatment had similar effects on the ability of trinitrophenol modified lymph node dendritic cells to stimulate the trinitrophenol specific hybridomas. Paraformaldehyde fixation and chloroquine treatment had similar effects on the ability of A20 cells to present ovalbumin to ovalbumin-specific hybridomas as they had on the ability of trinitrophenol modified A20 cells to present trinitrophenol to the trinitrophenol specific hybridomas. One of seven T-cell hybridomas responded to trinitrophenol modified ovalbumin but not other trinitrophenol modified proteins. These results suggest that, at least in part, T cells in the contact hypersensitivity response to trinitrophenol recognize antigens that require processing and that trinitrophenol modified proteins can be recognized

COVID-19 IDD: A global survey exploring the impact of COVID-19 on individuals with intellectual and developmental disabilities and their caregivers

Background: This protocol outlines research to explore the impact of coronavirus disease 2019 (COVID-19) on individuals who have intellectual and developmental disabilities and their caregivers. Evidence suggests that people with intellectual and developmental disabilities experience disparities in healthcare access and utilisation. This disparity was evident early in the pandemic when discussions arose regarding the potential exclusion of this population to critical care. Methods: An anonymous online survey will be conducted with caregivers, both family members and paid staff, to explore the impact of COVID-19 on this population in terms of demographics, living arrangements, access to services, the impact of social distancing, and also carer wellbeing. The survey will be developed by the research team, many of whom are experts in intellectual disability within their own jurisdictions. Using back-translation our team will translate the survey for distribution in 16 countries worldwide for international comparison. The survey team have extensive personal and professional networks in intellectual disability and will promote the survey widely on social media with the support of local disability and advocacy agencies. Statistical descriptive and comparative analyses will be conducted. Ethical approval has been obtained for this study from University College Dublin’s Human Research Ethics Committee (HS-20-28-Linehan). Dissemination: Study findings will be prepared in a number of formats in order to meet the needs of different audiences. Outputs will include academic papers, lessons learned paper, practice guidelines, reports, infographics and video content. These outputs will be directed to families, frontline and management delivering disability services, national-level policy makers, healthcare quality and delivery authorities, national pandemic organisations and international bodies

Professional Uncertainty and Disempowerment Responding to Ethnic Diversity in Health Care: A Qualitative Study

From a qualitative study, Joe Kai and colleagues have identified opportunities to empower health professionals to respond more effectively to challenges in their work with patients from diverse ethnic communities

Understanding and evaluating systematic reviews and meta-analyses

A systematic review is a summary of existing evidence that answers a specific clinical question, contains a thorough, unbiased search of the relevant literature, explicit criteria for assessing studies and structured presentation of the results. A systematic review that incorporates quantitative pooling of similar studies to produce an overall summary of treatment effects is a meta-analysis. A systematic review should have clear, focused clinical objectives containing four elements expressed through the acronym PICO ( Patient, group of patients, or problem, an Intervention, a Comparison intervention and specific O utcomes). Explicit and thorough search of the literature is a pre-requisite of any good systematic review. Reviews should have pre-defined explicit criteria for what studies would be included and the analysis should include only those studies that fit the inclusion criteria. The quality (risk of bias) of the primary studies should be critically appraised. Particularly the role of publication and language bias should be acknowledged and addressed by the review, whenever possible. Structured reporting of the results with quantitative pooling of the data must be attempted, whenever appropriate. The review should include interpretation of the data, including implications for clinical practice and further research. Overall, the current quality of reporting of systematic reviews remains highly variable

Preliminary functional analysis of human epidermal T cells

The function of human epidermal T cells (ETC) is unknown. In the present study, dermal T cells (DTC), ETC and keratinocytes were cultured from normal human skin, DTC and ETC lines were expanded in medium containing interleukin 2. The autologous keratinocytes were transfected with a human papillomavirus 16 E6 and E7 plasmid to produce an immortal keratinocyte line 'HEK001'. Lymphocyte migration and adhesion to HEK001 was assessed in calcein fluorimetric assays, ETC migrated towards HEK001 three to four times more than DTC. ETC adhered to HEK001 two to four times more than DTC. The proportion of ETC expressing the cutaneous lymphocyte-associated antigen was greater than that of DTC (26% and 1%, respectively). The keratinocyte line HEK001 expressed ICAM-1 following stimulation with TNF-α or IFN-γ and following coculture with autologous cutaneous T cells, A blocking anti-ICAM-1 antibody reduced DTC and ETC adhesion to HEK001 by 30% and 50%, respectively. Therefore, cutaneous T cells may upregulate keratinocyte ICAM-1 expression which mediates adhesion to autologous keratinocytes. These results are consistent with the hypothesis that the ETC and DTC populations are distinct. Both directed migration (epidermotropism) and selective retention may be involved in the development and maintenance of the ETC population in normal human skin