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Background: Anti-N-Methyl-d-aspartate receptor (NMDAR) autoimmune encephalitis (NMDAR AE) is an autoimmune disease characterized by severe psychiatric and neurological symptoms. While the pathogenic role of antibodies (Abs) directed against the GluN1 subunit of NMDAR is well described in this disease, the immune mechanisms involved in the generation of the autoimmune B cell response, especially the role of T helper cells, are poorly understood. Previously, we developed a B-cell-mediated mouse model of NMDAR AE by immunization with a GluN1359–378 peptide that drives a series of symptoms that recapitulate AE such as anxiety behaviour and spatial memory impairment. Results: In this mouse model, we identified anti-GluN1-specific CD4+ but also CD8+ T cells in both spleen and meninges. T helper cells have a polyfunctional profile, arguing for a T and B cell crosstalk to generate anti-GluN1 pathogenic Abs. Interestingly, proteomic analysis of AE meninges showed enrichment of differentially expressed proteins in biological processes associated with B cell activation and cytokine signalling pathways. Conclusions: This study identified, for the first time, a potential contribution of T helper cells in the pathology of NMDAR AE and paved the way for the development of future tolerogenic approaches to treat relapses. [ABSTRACT FROM AUTHOR]

Keywords: allergy; basophil activation test; diagnosis; standardisation EN allergy basophil activation test diagnosis standardisation 1055 1058 4 10/09/23 20231001 NES 231001 Key messages Adherence with guidelines was achieved for sample collection, transport and completion time. Priority needs for improvement are the standardisation of control validation and allergen concentrations tested. As mentioned by Eberlein et al.,[6] combinations of markers are needed for an accurate gating strategy; for example CCR3 SP + sp /CD3 SP neg sp , CRTH2 SP hi sp /CD3 SP neg sp , CD123 SP hi sp /HLA-DR SP neg sp or IgE SP + sp /CD203c SP + sp . ACKNOWLEDGEMENTS We thank the participants who completed the survey and the AllergoBioNet network for supporting the study: Dr Thierry Tabary, Dr Lorna Garnier, Dr Yannick Chantran, Dr Mylene De Saint Jore, Dr Claude Lambert, Dr Stéphanie Rogeau, Dr Moïse Michel, Dr Joana Vitte, Dr Martine Pernollet, Dr Jean Milhes, Dr Céline Beauvillain, Dr Béatrice Uring-Lambert, Dr Delphine Mariotte, Dr Mirjana Radosavljevic and Dr Pol André Apoil. [Extracted from the article]

After patients receive kidney transplants, they either receive immunosuppressive drugs such as cyclosporine and steroids, or an agent such as polyclonal antilymphocyte serum (a different immunosuppressant), followed by cyclosporine and steroids two weeks later. An advantage of the latter regimen is that it allows the graft to recover from ischemia (decreased blood supply) during the time when it is especially sensitive to the toxic effects of cyclosporine. A monoclonal antibody has been developed that selectively inactivates only those lymphocytes that act against donor antigens, and this could be useful as an alternative to antilymphocyte serum, since it is more specific and does not inactivate all T cells. The substance, 33B3.1, acts by interfering with binding of interleukin-2 to its receptor on the T cell, thereby preventing proliferation of T cells. Its effectiveness was tested in 100 patients receiving their first renal transplants, half of whom received 33B3.1, and half of whom received antithymocyte globulin in a randomized study. Other medications were also administered. Patients were followed-up 5 to 22 months. Rejection was assessed clinically and by biopsy, when necessary, in both groups. The severity of infection with cytomegalovirus was noted. Results showed that the new antibody was tolerated better than antithymocyte globulin, a large percentage of whose recipients discontinued treatment during the first 14 days. One patient could not tolerate 33B3.1. Differences between the groups in subsets of T cells were found, such that antithymocyte globulin patients had greater drops in their CD2-, CD3-, CD4-, and CD8-positive cell counts. There were more rejection episodes in the 33B3.1 group (six) than the antithymocyte group (one), although the difference was not statistically significant. There were no group differences in patient (96 percent) or graft (85 percent) survival. Fewer infections were noted in the 33B3.1 group, including urinary tract infections, but the incidence of cytomegalovirus was about the same in both groups. Overall, it appears that the interleukin-2 receptor is an appropriate target for an immunosuppressive agent, and that 33B3.1 is an effective compound in this regard. (Consumer Summary produced by Reliance Medical Information, Inc.)

Histamine is known to be stable in the plasma obtained after centrifugation up to 4 days at RT for patients and controls.9 According to these results, we suggest that whole blood samples can be stored at +4°C up to 72 hours for histamine and 7 days for tryptase when the laboratory is not available immediately. Tryptase release is considered a robust marker of mast cell degranulation but is not informative in mild reactions and often normal during food-induced allergic reactions.1 Histamine is released at the early beginning of the reaction and may be useful when tryptase levels are normal or not informative. Keywords: histamine; pre-analytic; tryptase; whole blood EN histamine pre-analytic tryptase whole blood 1579 1583 5 05/17/21 20210501 NES 210501 Immediate hypersensitivity reactions are related to mast cell and/or basophil activation. Increased tryptase is defined as >=1.2 × basal value + 2 µg.L SP -1 sp .4 In our hands, tryptase uncertainties of measurement for low and high concentrations (9 µg.L SP -1 sp and 38.2 µg.L SP -1 sp ) are 17% and 16%, respectively, in accordance with published results.5 Plasma histamine concentrations were measured by a radioimmunoassay (Beckman Coulter, ImmunoTech). [Extracted from the article]

CD4+ T cells differentiate into various T helper subsets characterized by distinct cytokine secreting profiles that confer them effector functions adapted to a variety of infectious or endogenous threats. Regulatory CD4+ T cells are another specialized subset that plays a fundamental role in the maintenance of immune tolerance to self-antigens. Manipulating effector or regulatory CD4+ T cells responses is a promising immunotherapy strategy for, respectively, chronical viral infections and cancer, or severe autoimmune diseases and transplantation. Adoptive cell therapy (ACT) is an emerging approach that necessitates defining robust and efficient methods for the in vitro expansion of antigen-specific T cells then infused into patients. To address this challenge, artificial antigen presenting cells (AAPCs) have been developed. They constitute a reliable and easily usable platform to stimulate and amplify antigen-specific CD4+ T cells. Here, we review the recent advances in understanding the functions of CD4+ T cells in immunity and in immune tolerance, and their use for ACT. We also describe the characteristics of different AAPC models and the way to improve their stimulating functions. Finally, we discuss the potential interest of these AAPCs, both as fundamental tools to decipher CD4+ T cell responses and as reagents to generate clinical grade antigen-specific CD4+ T cells for immunotherapy. [ABSTRACT FROM AUTHOR]

Gamma-delta (γδ) T cells contribute to the innate immune response against cancer. In samples of 20 patients upon DLBCL diagnosis, we found that Vδ1+T cells were the major γδ T cell subset in tumors and PBMCs of patients, while Vδ2 T cells were preponderant in PBMCs of healthy subjects. Interestingly, the germinal center (GC) subtype was associated with an increase in Vδ1+T cells in tumors, whereas the non-GC subtype was associated with a lower frequency of γδ T cells. While circulating Vδ1+T cells of patients or HSs mostly exhibited a naïve phenotype, the majority of tumor Vδ1+T cells showed a central memory phenotype. Resident or circulating γδ T cells from patients were not functionally impaired since they produced high levels of IFN-γ. Collectively, our findings are in favor of γδ T cell activation in tumors and open new perspectives for their modulation in DLBCL immunotherapy. [ABSTRACT FROM AUTHOR]

Owing to their multiple immune functions, CD4+ T cells are of major interest for immunotherapy in chronic viral infections and cancer, as well as for severe autoimmune diseases and transplantation. Therefore, standardized methods allowing rapid generation of a large number of CD4+ T cells for adoptive immunotherapy are still awaited. We constructed stable artificial antigen‐presenting cells (AAPCs) derived from mouse fibroblasts. They were genetically modified to express human leukocyte antigen (HLA)‐DR molecules and the human accessory molecules B7.1, Intercellular adhesion molecule‐1 (ICAM‐1) and lymphocyte function‐associated antigen‐3 (LFA‐3). AAPCs expressing HLA‐DR1, HLA‐DR15 or HLA‐DR51 molecules and loaded with peptides derived from influenza hemagglutinin (HA), myelin basic protein (MBP) or factor VIII, respectively, activated specific CD4+ T‐cell clones more effectively than Epstein‐Barr virus (EBV)‐transformed B cells. We also showed that AAPCs were able to take up and process whole Ag proteins, and present epitopes to specific T cells. In primary cultures, AAPCs loaded with HA peptide allowed generation of specific Th1 lymphocytes from healthy donors as demonstrated by tetramer and intracellular cytokine staining. Although AAPCs were less effective than autologous peripheral blood mononuclear cells (PBMCs) to stimulate CD4+ T cells in primary culture, AAPCs were more potent to reactivate and expand memory Th1 cells in a strictly Ag‐dependent manner. As the availability of autologous APCs is limited, the AAPC system represents a stable and reliable tool to achieve clinically relevant numbers of CD4+ T cells for adoptive immunotherapy. For fundamental research in immunology, AAPCs are also useful to decipher mechanisms involved in the development of human CD4 T‐cell responses. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing the prevalence of monoclonal gammopathy of undetermined significance among farmers in France.