Notch 2 receptor expression and reduced cytotoxicity in MAIT cells of active pulmonary TB patients.

BACKGROUND: Knowledge of the prevalence of common sensitizing allergens may aid in overall management of allergic disease in a specified area. OBJECTIVE: The aim of this study was to identify and analyse the prevalence of common inhaled and food sensitizing allergens in Beijing. METHODS: This was a retrospective study, analysing demographic data and serum sIgE antibody test results from 59057 outpatients who presented to Beijing TongRen Hospital, from January 2013 to December 2019. RESULTS: 28879 patients (48.9%) showed positive sIgE test results; with significantly more males aged under 16 years sensitized to at least one allergen than females, and most patients (53.62%) were sensitized to multiple allergens. The first inhaled sensitizing allergens was Artemisia grass (11910 (41.24%)); and the first food allergens was crab (3547 (12.28%)). For Artemisia sensitized patients, sIgE levels were mostly at level 5. The number of patients with ragweed allergy is increasing year by year. The detection rates for sIgE to Artemisia, common ragweed, and Humulus grass allergens were significantly higher in August and September. R package ggplot2 analysis, demonstrated strong correlations between tree allergens and common ragweed and Humulus grass allergens (phi coefficients = 0.50 and 0.46, respectively; both P < 0.01). CONCLUSIONS: The prevalence of sensitization to different allergens in Beijing showed Artemisia grass was the most commonly inhaled sensitizing allergen, and the number of patients with ragweed grass allergy was increasing by year.

TIL expansion with high dose IL-2 or low dose IL-2 with anti-CD3/anti-CD28 stimulation provides different quality of TIL-expanded T cell clones.

Tumor infiltrating lymphocytes (TILs) are cells that are present inside the tumor environment, of which include T cells, B cells and natural killer (NK) cells. At present, TILs are used for immunotherapy in various cancers. Knowledge on adoptive transfer of TILs in ovarian cancer is still limited, especially regarding TIL expansion methods. Therefore, the aim of our study was to compare the quality of T cell clones between two expansion methods for ovarian cancer TILs. We show that TILs stimulated with the mitogenic stimulation method (low dose IL-2 with anti-human CD3/CD28) and the standard stimulation method (high dose IL-2 only) both increased total number of T cells. TCR repertoire analyses revealed different TCR repertoire patterns between TIL-expanded T cells that were stimulated with the standard stimulation method (high dose IL-2 only) and the mitogenic stimulation method (low dose IL-2 with anti-human CD3/CD28). Regardless, when TILs were expanded using the standard stimulation method (high dose IL-2 only), the predominant T cell receptor beta variable (TRBV) chains that were used in both TIL-expanded clones of the CD4+ and CD8+ subpopulations were similar. In addition, there were also TIL-expanded CD4+ and CD8+ T cell clones that were dominant in only one or the other subpopulations. These results reveal the bias in TIL quality after being stimulated with different protocols. Further studies are required to understand the selection of TIL expansion, in order for a more efficacy adoptive transfer treatment.

The infrapatellar fat pad produces interleukin-6-secreting T cells in response to a proteoglycan aggrecan peptide and provides dominant soluble mediators different from that present in synovial fluid.

OBJECTIVE: The purpose of this study was to investigate the effects of osteoarthritis (OA) peripheral blood mononuclear cell (PBMC) -stimulating proteoglycan aggrecan peptides on T cells present in infrapatellar fat pads (IPFPs) and synovial tissues, and to correlate these findings with mediators present in synovial fluid of OA patients. METHODS: We tested for interleukin-6 (IL-6) -producing T cells in IPFPs of patients with knee OA using ELISPOT. Cytokine and cytotoxic mediator production from OA PBMCs, IPFPs, synovial tissues, and synovial fluids in response to proteoglycan aggrecan peptides were quantified by cytometric bead array. Patterns of cytokine and cytotoxic mediator production were analyzed and compared. RESULTS: T cells from IPFPs elicited strong responses towards the p263-280 peptide by secreting IL-6. In addition, there was a trend that the p263-280 peptide stimulated higher production of cytokines/cytotoxic mediators than other proteoglycan aggrecan peptides, although this was not statistically significant. In patients with knee OA, a group of cytotoxic mediators (sFas, perforin, granzyme A, and granulysin) and IL-6 were detectable at high levels from the synovial fluid. In addition, inflammation in patients with knee OA was more pronounced in joint-surrounding tissues than levels in circulating peripheral blood. CONCLUSION: Our data suggest that T cells responding to the p263-280 peptide contribute to the secretion of various soluble mediators that are found within the synovial fluid. We also identified potential new candidates that may serve as biomarkers of knee OA.

Functional and T Cell Receptor Repertoire Analyses of Peripheral Blood and Infrapatellar Fat Pad T Cells in Knee Osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a condition that features inflammation and immune responses of innate and adaptive immunity. The role of T cells in knee OA pathogenesis is still unclear. Our aim was to characterize T cell functions and their clonality in patients with knee OA in peripheral blood (PB) and infrapatellar fat pads (IPFP). METHODS: We isolated T cells from PB and IPFP of patients with knee OA and PB of healthy individuals and determined soluble mediators produced from these cells. In addition, we performed a clonal analysis of activated CD8+ T cells and compared the T cell receptor ß-variable gene chain (TRBV) usages between T cells in PB and IPFP of patients with knee OA. RESULTS: Our results suggest that in patients with knee OA, circulating T cells possess a more "cytotoxic" profile or rather impaired cytokine production, but the knee microenvironment allows for these T cells to produce proinflammatory cytokines [interleukin (IL)-1ß, IL-6, tumor necrosis factor], IL-17, and interferon-γ within IPFP. Activated CD8+ IPFP T cells carry different repertoire distribution from those present in PB of patients with knee OA. Shared TRBV usage of activated CD8+ IPFP T cells among the 3 patients with knee OA was also observed. CONCLUSION: Our study describes the nature of T cells in knee OA that may be due to "unhealthy" aging or other factors that drive healthy aging T cells into a state of imbalance, thus contributing to the pathogenesis of knee OA.