European Journal of Immunology最新文献

Infection with SARS-CoV-2 results in mild to severe COVID-19 disease courses. Several studies showed the association of impaired T-cell responses and certain HLA haplotypes with disease severity. However, it remained unclear if T-cell activation was compromised due to a general reduction of presented epitopes or other intrinsic factors within APCs or T cells. Furthermore, a potential reduction of presented epitopes would suggest if an upcoming SARS-CoV-2 variant could escape T-cell immunity. Hence, knowledge about the T-cell epitope landscape of SARS-CoV-2 would allow to better understand mechanisms leading to severe disease and to estimate the potential stability of the T-cell response in light of virus evolution, which might provide insights for future vaccine designs. Hence, in the present study, the T-cell epitope landscape of SARS-CoV-2 was determined via in vitro T-cell stimulation plus in silico prediction. HLAs associated with mild and severe disease courses showed almost the same potential in epitope presentation, suggesting intrinsic factors of APCs or T cells as contributors to the more severe disease courses. As T-cell epitopes did also not originate from regions of SARS-CoV-2 having shown high mutation rates in the past, a relatively stable T-cell response can be expected regarding new SARS-CoV-2 strains in the future. Analysis of the T-cell epitope landscape of SARS-CoV-2 suggests T-cell intrinsic factors as likely modulators of disease severity and that the capacity of MHC-peptide presentation remains stable among circulating SARS-CoV-2 viral strains.

Nonobese diabetic (NOD) mice are a widely used animal model to study mechanisms leading to autoimmune diabetes. A gluten-free diet reduces and delays the incidence of diabetes in NOD mice, but the underlying mechanisms remain largely unknown. In this study, we performed single-cell transcriptomic and flow cytometry analysis of T cells and innate lymphocytes in the spleen and pancreatic lymph nodes of NOD mice fed a gluten-free or standard diet. We observed that the gluten-free diet did not induce a substantial alteration in the abundance or phenotype of any lymphocyte subset that would directly explain its protective effect against diabetes. However, the gluten-free diet induced subtle changes in the differentiation of subsets with previously proposed protective roles in diabetes development, such as Tregs, activated γδT cells, and NKT cells. Globally, the gluten-free diet paradoxically promoted activation and effector differentiation across multiple subpopulations and induced genes regulated by IL-2, IL-7, and IL-15. In contrast, the standard diet induced type I interferon-responsive genes. Overall, the gluten-free diet might prevent diabetes in NOD mice by inducing small-scale changes in multiple cell types rather than acting on a specific lymphocyte subset.

In children with chronic non-bacterial osteomyelitis, clinical and transcriptional changes in peripheral blood were examined after pamidronate treatment. Clinically effective treatment with pamidronate was associated with reduced expression of two genes (TRDV2 and TRGV9) that encode the subunits of the Vγ9Vδ2 T-cell receptor.

The immune system (IS) is commonly understood as a system composed of specific cells and tissues that have evolved to contrast pathogens and defend the host. By virtue of this capacity, it has come to be considered capable of making an essential distinction, that between self versus non-self, which would contribute to a clear identity of the organism. However, in the wake of evolution and ecology, growing evidence suggests that the so-called immune system, which also evolved from symbiotic interactions with external agents, is not just a defensive system that merely protects the organism but, on the contrary, is involved in many global regulatory and homeostatic functions. Moreover, in performing these many functions, IS is not only an ensemble of host cells and tissues but functionally is constitutively determined by the interaction with a set of associated microorganisms, that is, the human microbiome. In this scenario, it is open-and-shut that the microbiome itself is a functional part of this extended immune system. Organisms and microbiomes together, therefore, form a functional whole, which constitutes a privileged form of biological organization. In light of this evidence showing the inadequacy of traditional accounts, we propose to extend and supplement the current IS conceptualization by introducing the notion of the symmunobiome. With this term, we intend to characterize the microbiome's own and unavoidable component to overall immune functionality. Therefore, we suggest a new immune system determination, articulated in three linked pillars—adaptive immunity, innate immunity, and symmunobiome—to better grasp the diverse functionality of extended immunity.

A key feature of cytotoxic CD8⁺ T cells for eliminating pathogens and malignant cells is their capacity to produce proinflammatory cytokines, which include TNF and IFNγ. Provided that these cytokines are highly toxic, a tight control of their production is imperative. RNA-binding proteins (RBPs) are essential for the fine-tuning of cytokine production. The role of the RBP ZFP36L1 and its sister protein ZFP36L2 herein has been established, but their relative contribution to cytokine production is not well understood. We here compared the effect of ZFP36L1 and ZFP36L2 single and double deficiency in murine effector CD8⁺ T cells. Whereas single deficient T cells significantly increased cytokine production, double deficiency completely unleashed the cytokine production. Not only the TNF production was substantially prolonged in double-deficient T cells. Also, the production of IFNγ reached unprecedented levels with >90% IFNγ-producing T cells compared with 3% in WT T cells after 3 days of continuous activation. This continuous cytokine production by double-deficient T cells was also observed in tumor-infiltrating lymphocytes in vivo, however, with no effect on tumor growth. ZFP36L1 and ZFP36L2 double deficiency resulted in decreased cell viability, impaired STAT5 signaling, and dysregulated cell cycle progression. In conclusion, while combined deletion in ZFP36L1 and ZFP36L2 can drive continuous cytokine production even upon chronic activation, safeguards are in place to counteract such super-cytokine producers.

Autoantibodies neutralizing Type I interferons increase the risk of severe viral diseases and are linked to autoimmune conditions. The automated VIDAS assay is suitable for anti-IFN-α2 IgGs quantification, offering a swift, reliable, user-friendly, single test for clinical management.

The fate of immune cells is fundamentally linked to their metabolic program, which is also influenced by the metabolic landscape of their environment. The tumor microenvironment represents a unique system for intercellular metabolic interactions, where tumor-derived metabolites suppress effector CD8⁺ T cells and promote tumor-promoting macrophages, reinforcing an immune-suppressive niche. This review will discuss recent advancements in metabolism research, exploring the interplay between various metabolites and their effects on immune cells within the tumor microenvironment.