Parallel detection of SARS-CoV-2 epitopes reveals dynamic immunodominance profiles of CD8 T memory cells in convalescent COVID-19 donors.

Objectives: High-magnitude CD8 T cell responses are associated with mild COVID-19 disease; however, the underlying characteristics that define CD8 T cell-mediated protection are not well understood. The antigenic breadth and the immunodominance hierarchies of epitope-specific CD8 T cells remain largely unexplored and are essential for the development of next-generation broad-protective vaccines. This study identified a broad spectrum of conserved SARS-CoV-2 CD8 T cell epitopes and defined their respective immunodominance and phenotypic profiles following SARS-CoV-2 infection.

T-cells in human trigeminal ganglia express canonical tissue-resident memory T-cell markers.

Background: Trigeminal ganglia (TG) neurons are the main site of lifelong latent herpes simplex virus type 1 (HSV-1) infection. T-cells in ganglia contribute to long-term control of latent HSV-1 infection, but it is unclear whether these cells are bona fide tissue-resident memory T-cells (T). We optimized the processing of human post-mortem nervous tissue to accurately phenotype T-cells in human TG ex vivo and in situ.

Organoids as tools for fundamental discovery and translation-a Keystone Symposia report.

Complex three-dimensional in vitro organ-like models, or organoids, offer a unique biological tool with distinct advantages over two-dimensional cell culture systems, which can be too simplistic, and animal models, which can be too complex and may fail to recapitulate human physiology and pathology. Significant progress has been made in driving stem cells to differentiate into different organoid types, though several challenges remain. For example, many organoid models suffer from high heterogeneity, and it can be difficult to fully incorporate the complexity of in vivo tissue and organ development to faithfully reproduce human biology.

Two sides of the same coin: Protective versus pathogenic CD4 resident memory T cells.

The ability of the adaptive immune system to form memory is key to providing protection against secondary infections. Resident memory T cells (T) are specialized T cell populations that reside within tissue sites where they await reencounter with their cognate antigen. T are distinct from circulating memory cells, including central and effector memory T cells, both functionally and transcriptionally.

Allo-reactive tissue-resident T cells causing damage: An inside job.

Tissue-resident memory T cells (TRM cells) reside in the epithelium and contribute to the first line defense against invading pathogens. Snyder et al. (2022.

The endothelial diapedesis synapse regulates transcellular migration of human T lymphocytes in a CX3CL1- and SNAP23-dependent manner.

Understanding how cytotoxic T lymphocytes (CTLs) efficiently leave the circulation to target cancer cells or contribute to inflammation is of high medical interest. Here, we demonstrate that human central memory CTLs cross the endothelium in a predominantly paracellular fashion, whereas effector and effector memory CTLs cross the endothelium preferably in a transcellular fashion. We find that effector CTLs show a round morphology upon adhesion and induce a synapse-like interaction with the endothelium where ICAM-1 is distributed at the periphery.

How to Reliably Define Human CD8 T-Cell Subsets: Markers Playing Tricks.

In recent years, our understanding about the functional complexity of CD8 T-cell populations has increased tremendously. The immunology field is now facing challenges to translate these insights into phenotypic definitions that correlate reliably with distinct functional traits. This is key to adequately monitor and understand compound immune responses including vaccination and immunotherapy regimens.

Divergent SARS-CoV-2-specific T- and B-cell responses in severe but not mild COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. Understanding the immune response that provides specific immunity but may also lead to immunopathology is crucial for the design of potential preventive and therapeutic strategies. Here, we characterized and quantified SARS-CoV-2-specific immune responses in patients with different clinical courses.

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells.

Blimp-1 Rather Than Hobit Drives the Formation of Tissue-Resident Memory CD8 T Cells in the Lungs.

Tissue-resident memory CD8 T (T) cells that develop in the epithelia at portals of pathogen entry are important for improved protection against re-infection. CD8 T cells within the skin and the small intestine are long-lived and maintained independently of circulating memory CD8 T cells. In contrast to CD8 T cells at these sites, CD8 T cells that arise after influenza virus infection within the lungs display high turnover and require constant recruitment from the circulating memory pool for long-term persistence.

Peripheral and systemic antigens elicit an expandable pool of resident memory CD8 T cells in the bone marrow.

BM has been put forward as a major reservoir for memory CD8  T cells. In order to fulfill that function, BM should "store" memory CD8 T cells, which in biological terms would require these "stored" memory cells to be in disequilibrium with the circulatory pool. This issue is a matter of ongoing debate.

Expression of IL-7Rα and KLRG1 defines functionally distinct CD8 T-cell populations in humans.

During acute viral infections in mice, IL-7Rα and KLRG1 together are used to distinguish the short-lived effector cells (SLEC; IL-7Rα KLRG ) from the precursors of persisting memory cells (MPEC; IL-7Rα KLRG1 ). We here show that these markers can be used to define distinct subsets in the circulation and lymph nodes during the acute phase and in "steady state" in humans. In contrast to the T cells in the circulation, T cells derived from lymph nodes hardly contain any KLRG1-expressing cells.

Functional Heterogeneity of CD4 Tumor-Infiltrating Lymphocytes With a Resident Memory Phenotype in NSCLC.

Resident memory T cells (T) inhabit peripheral tissues and are critical for protection against localized infections. Recently, it has become evident that CD103 T are not only important in combating secondary infections, but also for the elimination of tumor cells. In several solid cancers, intratumoral CD103CD8 tumor infiltrating lymphocytes (TILs), with T properties, are a positive prognostic marker.

Tissue-resident memory T cells populate the human brain.

Most tissues are populated by tissue-resident memory T cells (T cells), which are adapted to their niche and appear to be indispensable for local protection against pathogens. Here we show that human white matter-derived brain CD8 T cells can be subsetted into CD103CD69 and CD103CD69 T cells both with a phenotypic and transcription factor profile consistent with T cells. Specifically, CD103 expression in brain CD8 T cells correlates with reduced expression of differentiation markers, increased expression of tissue-homing chemokine receptors, intermediate and low expression of the transcription factors T-bet and eomes, increased expression of PD-1 and CTLA-4, and low expression of cytolytic enzymes with preserved polyfunctionality upon activation.

Blimp-1 induces and Hobit maintains the cytotoxic mediator granzyme B in CD8 T cells.

CD8 T cells acquire cytotoxic molecules including granzyme B during effector differentiation. Both tissue-resident memory CD8 T cells (Trm) and circulating CD45RA effector-type T cells (Temra) cells have the ability to retain granzyme B protein expression into the memory phase, but it is unclear how this persistence of cytolytic activity is regulated during steady state. Previously, we have described that the transcriptional regulators Hobit and Blimp-1 have overlapping target genes that include granzyme B, but their impact on the regulation of cytotoxicity in Trm and Temra cells during homeostasis has remained unclear.

Tissue-resident memory T cells at the center of immunity to solid tumors.

Immune responses in tissues are constrained by the physiological properties of the tissue involved. Tissue-resident memory T cells (T cells) are a recently discovered lineage of T cells specialized for life and function within tissues. Emerging evidence has shown that T cells have a special role in the control of solid tumors.

The Fate Choice Between Effector and Memory T Cell Lineages: Asymmetry, Signal Integration, and Feedback to Create Bistability.

CD8 T cells clear primary infections with intracellular pathogens and provide long-term immunity against reinfection. Two different types of CD8 T cells are responsible for these functions: short-lived effector T cells and memory T cells. The cellular relationship between these two types of CD8 T cells has been subject to much investigation.

Specific T Cell Responses against Minor Histocompatibility Antigens Cannot Generally Be Explained by Absence of Their Allelic Counterparts on the Cell Surface.

Allogeneic stem cell transplantation has emerged as immunotherapy in the treatment of a variety of hematological malignancies. Its efficacy depends on induction of graft versus leukemia by donor lymphocytes. Both graft versus leukemia and graft versus host disease are induced by T cells reactive against polymorphic peptides, called minor histocompatibility antigens (MiHA), which differ between patient and donor and are presented in the context of self-HLA (where HLA is human leukocyte antigen).

The Transcription Factor Hobit Identifies Human Cytotoxic CD4 T Cells.

The T cell lineage is commonly divided into CD4-expressing helper T cells that polarize immune responses through cytokine secretion and CD8-expressing cytotoxic T cells that eliminate infected target cells by virtue of the release of cytotoxic molecules. Recently, a population of CD4 T cells that conforms to the phenotype of cytotoxic CD8 T cells has received increased recognition. These cytotoxic CD4 T cells display constitutive expression of granzyme B and perforin at the protein level and mediate HLA class II-dependent killing of target cells.

TCR-based therapy for multiple myeloma and other B-cell malignancies targeting intracellular transcription factor BOB1.

Immunotherapy for hematological malignancies or solid tumors by administration of monoclonal antibodies or T cells engineered to express chimeric antigen receptors or T-cell receptors (TCRs) has demonstrated clinical efficacy. However, antigen-loss tumor escape variants and the absence of currently targeted antigens on several malignancies hamper the widespread application of immunotherapy. We have isolated a TCR targeting a peptide of the intracellular B cell-specific transcription factor BOB1 presented in the context of HLA-B*07:02.

Pulmonary immune responses against Aspergillus fumigatus are characterized by high frequencies of IL-17 producing T-cells.

Unlabelled: In healthy individuals and in patients with invasive aspergillosis, Aspergillus-specific T-cells in peripheral blood display mainly a Thelper1 phenotype. Although in other fungal infections Thelper17 immunity is important, it was suggested that in aspergillus infection Thelper17 cells do not play a role or may even be detrimental.

Objectives: To compare the cytokine profiles of Aspergillus-specific CD4+ T-cells in peripheral blood and in the lung.

Programs for the persistence, vigilance and control of human CD8 lung-resident memory T cells.

Tissue-resident memory T cells (T cells) in the airways mediate protection against respiratory infection. We characterized T cells expressing integrin α (CD103) that reside within the epithelial barrier of human lungs. These cells had specialized profiles of chemokine receptors and adhesion molecules, consistent with their unique localization.