High-resolution repertoire analysis reveals a major bystander activation of Tfh and Tfr cells.

T follicular helper (Tfh) and regulatory (Tfr) cells are terminally differentiated cells found in germinal centers (GCs), specialized secondary lymphoid organ structures dedicated to antibody production. As such, follicular T (Tfol) cells are supposed to be specific for immunizing antigens, which has been reported for Tfh cells but is debated for Tfr cells. Here, we used high-throughput T cell receptor (TCR) sequencing to analyze the repertoires of Tfh and Tfr cells, at homeostasis and after immunization with self- or foreign antigens. We observed that, whatever the conditions, Tfh and Tfr cell repertoires are less diverse than those of effector T cells and Treg cells of the same tissues; surprisingly, these repertoires still represent thousands of different sequences, even after immunization with a single antigen that induces a 10-fold increase in Tfol cell numbers. Thorough analysis of the sharing and network of TCR sequences revealed that a specific response to the immunizing antigen can only, but hardly, be detected in Tfh cells immunized with a foreign antigen and Tfr cells immunized with a self-antigen. These antigen-specific responses are obscured by a global stimulation of Tfh and Tfr cells that appears to be antigen-independent. Altogether, our results suggest a major bystander Tfol cell activation during the immune response in the GCs.

Effectiveness of behavior change in rehabilitation interventions to improve functional recovery after lower limb fracture: a systematic review.

Ankle fractures are common injuries that can significantly impact mobility and quality of life. Rehabilitation following ankle fracture treatment is crucial for recovery, yet adherence to regimens remains a challenge. Behaviour Change Techniques (BCTs) have been suggested to improve adherence, but their effectiveness in ankle fracture rehabilitation is not well established. This review aimed to evaluate the effectiveness of BCTs in the rehabilitation of ankle fracture patients. We conducted a comprehensive search across multiple databases, including MEDLINE and EMBASE, focusing on Randomised Controlled Trials (RCTs) that incorporated BCTs into rehabilitation interventions. The effectiveness of BCTs on patient-reported outcomes (PROMs), quality of life, and adverse events was analysed. Nine RCTs met the inclusion criteria, encompassing a range of interventions that employed BCTs, most commonly including goal setting and instruction on how to perform behaviours, specifically physiotherapy exercises. The review found limited evidence supporting their effectiveness in improving PROMs. Only one study showed a significant positive effect, but it was deemed at high risk of bias. The lack of integration of behavioural theory in the design of rehabilitation interventions and the varied nature of the BCTs employed across studies may contribute to these findings. The use of BCTs in ankle fracture rehabilitation is prevalent, but this review highlights a significant gap their role of enhancing patient outcomes. Future research should incorporate a theory-based approach to intervention design, utilising a broader range of BCTs, to fully evaluate their potential in improving rehabilitation adherence and outcomes following ankle fracture .