Immunological Reviews最新文献

Cardiovascular diseases (CVD) are shaped by a complex interplay with immune mechanisms. In particular, the distinct roles of antigen-specific T cell mechanisms are emerging as critical determinants across a broad spectrum of conditions, ranging from atherosclerosis, myocardial infarction (MI), heart failure (HF), and myocarditis. Because these T cell responses are fundamentally driven by antigen recognition of cardiovascular antigens, understanding T cell clonal dynamics via accessing T cell receptor (TCR) repertoires might provide valuable mechanistic insights for developing targeted diagnostic and therapeutic immunomodulatory approaches in cardiology. In this review, we discuss T cell-dependent mechanisms and TCR clonal dynamics across various CVD. Moreover, by curating public bulk and single-cell TCR datasets across different etiologies, we present a first-in-class adaptive immune receptor database in cardiovascular diseases (CVD-TCR database). The discussions and resources herein presented seek to promote an integrated understanding of tissue-specific immune mechanisms across different CVD, facilitate the identification of shared clonotypes and motifs, and provide a framework for computational modeling of TCR repertoires across the CVD spectrum.

The thymic medulla is essential for establishing central tolerance, orchestrating the development of a diverse yet self-tolerant T cell repertoire, and preventing autoimmunity. This process is primarily mediated through interactions between developing thymocytes and antigen-presenting cells, including thymic epithelial cells (TECs) and dendritic cells (DCs), with additional regulatory contributions from endothelial cells, mesenchymal cells, and macrophages. Despite its critical role, the complexity of late-stage thymocyte development and the dynamics of their medullary residency remain incompletely understood. Recent advances in single-cell, epigenomic, and transcriptomic technologies have begun to reveal previously unappreciated layers of cellular and molecular heterogeneity within the thymic medulla throughout life. In this review, we explore how the medulla shapes the fate of both conventional and non-conventional T cells, examine the diversity of thymocyte populations it supports, and discuss how this specialized microenvironment adapts during aging and regeneration.

Multiple sclerosis (MS) is a T helper (Th) cell-mediated disease that targets central nervous system (CNS) white matter. This disease affects three times more females than males. For many years, the etiology of MS was not well understood and the exact nature of the autoimmune reaction was speculative. It has now become clear that MS is a rare complication of Epstein–Barr Virus (EBV) infection and that the virus induces an EBV nuclear antigen (EBNA-1)-specific T and B cell response that is cross-reactive against a number of CNS antigens including Glial cell-associated membrane protein (GlialCAM), Anoctamin-2 (Ano-2), myelin basic protein (MBP), and alpha-B-crystallin (CRYAB). Recent studies have clarified the involvement of the major human leukocyte antigen (HLA) MS risk haplotype, HLA-DR15, in sustaining autoreactive T cell responses and its interaction with EBV. Here, we overview this literature through the lens that MS is a disease that affects females more than males. We describe how EBV seroprevalence and the incidence of infectious mononucleosis are greater in females during the early teen years, a period of increased MS susceptibility. We overview how females with MS develop greater levels of EBNA-1-cross-reactive autoantibodies and show greater myelin-specific T helper 1 (Th1) cells in peripheral blood. Finally, we provide evidence that EBV-infected B cells may achieve a greater state of latency in females and discuss how this may perpetuate CNS autoimmunity. At the same time, our literature search identified many missed opportunities to learn about sex differences in MS. Our hope is that this review will motivate researchers in the future to disaggregate data by sex to accelerate discoveries in this disease.

Food allergen-specific IgE can cause significant pathology, yet the pathways that generate pathogenic, high-affinity IgE remain incompletely understood. Increasing evidence suggests that IgE responses arise from the integration of multiple, and sometimes opposing, T cell–derived cues. T follicular helper (Tfh) cells shape affinity maturation within germinal centers and likely coordinate class switching, while tissue-resident Th2 cells amplify local inflammation and potentially reinforce IgE production. Distinct Tfh subsets, characterized by differential production of IL-4 and IL-13, may further determine whether IgE responses remain low-affinity or mature into high-affinity antibodies capable of driving anaphylaxis. At the same time, regulatory populations—including regulatory T (Treg) cells and T follicular regulatory (Tfr) cells—impose restraints that can dampen or redirect humoral immunity. Early-life antigen exposure may tip this balance toward durable tolerance or toward progressive diversification of pathogenic IgE. Together, these mixed signals from helper, regulatory, and innate-like T cells likely determine the magnitude, affinity, and clinical impact of IgE responses. In this review, we explore how these intersecting pathways collectively regulate IgE immunity.