Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent infection.

Chronic infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation.

Resident Memory T Cells in the Atherosclerotic Lesion Associate With Reduced Macrophage Content and Increased Lesion Stability.

Background: Tissue resident memory T (T) cells are a T-cell subset that resides at the site of prior antigen recognition to protect the body against reoccurring encounters. Besides their protective function, T cells have also been implicated in inflammatory disorders. T cells are characterized by the expression of CD69 and transcription factors Hobit (homolog of Blimp-1 [B lymphocyte-induced maturation protein 1] in T cells) and Blimp-1.

Intestinal tissue-resident memory T cells maintain distinct identity from circulating memory T cells after in vitro restimulation.

Resident memory T (T) cells have been recently established as an important subset of memory T cells that provide early and essential protection against reinfection in the absence of circulating memory T cells. Recent findings showing that T expand in vivo after repeated antigenic stimulation indicate that these memory T cells are not terminally differentiated. This suggests an opportunity for in vitro T expansion to apply in an immunotherapy setting.

The adhesion G protein-coupled receptor GPR56/ADGRG1 in cytotoxic lymphocytes.

GPR56/ADGRG1 is an adhesion G protein-coupled receptor connected to brain development, haematopoiesis, male fertility, and tumorigenesis. Nevertheless, expression of GPR56 is not restricted to developmental processes. Studies over the last years have demonstrated a marked presence of GPR56 in human cytotoxic NK and T cells.

No-shows in T-cell responses are frequent for clones of low T-cell receptor affinity.

The magnitude of CD8 T-cell responses against intracellular pathogens is thought to primarily depend on the expansion capacity of naïve T cells, given that their recruitment is considered optimal. In the current issue of the European Journal of Immunology [Eur. J.

Memory CD8 T cells upregulate glycolysis and effector functions under limiting oxygen conditions.

Memory CD8 T cells are indispensable for maintaining long-term immunity against intracellular pathogens and tumors. Despite their presence at oxygen-deprived infected tissue sites or in tumors, the impact of local oxygen pressure on memory CD8 T cells remains largely unclear. We sought to elucidate how oxygen pressure impacts memory CD8 T cells arising after infection with Listeria monocytogenes-OVA.

ILC1: Development, maturation, and transcriptional regulation.

Type 1 Innate Lymphoid cells (ILC1s) are tissue-resident cells that partake in the regulation of inflammation and homeostasis. A major feature of ILC1s is their ability to rapidly respond after infections. The effector repertoire of ILC1s includes the pro-inflammatory cytokines IFN-γ and TNF-α and cytotoxic mediators such as granzymes, which enable ILC1s to establish immune responses and to directly kill target cells.

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.

A third vaccination with a single T cell epitope confers protection in a murine model of SARS-CoV-2 infection.

Understanding the mechanisms and impact of booster vaccinations are essential in the design and delivery of vaccination programs. Here we show that a three dose regimen of a synthetic peptide vaccine elicits an accruing CD8 T cell response against one SARS-CoV-2 Spike epitope. We see protection against lethal SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model in the absence of neutralizing antibodies, but two dose approaches are insufficient to confer protection.

Hobit and Blimp-1 regulate T abundance after LCMV infection by suppressing tissue exit pathways of T precursors.

Tissue-resident memory T cells (Trm) are retained in peripheral tissues after infection for enhanced protection against secondary encounter with the same pathogen. We have previously shown that the transcription factor Hobit and its homolog Blimp-1 drive Trm development after viral infection, but how and when these transcription factors mediate Trm formation remains poorly understood. In particular, the major impact of Blimp-1 in regulating several aspects of effector T-cell differentiation impairs study of its specific role in Trm development.

Tissue-resident memory T cells in the urogenital tract.

Our understanding of T cell memory responses changed drastically with the discovery that specialized T cell memory populations reside within peripheral tissues at key pathogen entry sites. These tissue-resident memory T (T) cells can respond promptly to an infection without the need for migration, proliferation or differentiation. This rapid and local deployment of effector functions maximizes the ability of T cells to eliminate pathogens.

Hyperglycemia and Not Hyperinsulinemia Mediates Diabetes-Induced Memory CD8 T-Cell Dysfunction.

Type 2 diabetes (T2D) causes an increased risk of morbidity and mortality in response to viral infection. T2D is characterized by hyperglycemia and is typically associated with insulin resistance and compensatory hyperinsulinemia. CD8 T cells express the insulin receptor, and previously, we have shown that insulin is able to directly modulate effector CD8 T-cell function.

Hobit and Blimp-1 instruct the differentiation of iNKT cells into resident-phenotype lymphocytes after lineage commitment.

iNKT cells are CD1d-restricted T cells that play a pro-inflammatory or regulatory role in infectious and autoimmune diseases. Thymic precursors of iNKT cells eventually develop into distinct iNKT1, iNKT2, and iNKT17 lineages in the periphery. It remains unclear whether iNKT cells retain developmental potential after lineage commitment.

The Inhibitory Receptor GPR56 () Is Specifically Expressed by Tissue-Resident Memory T Cells in Mice But Dispensable for Their Differentiation and Function In Vivo.

Tissue-resident memory T (T) cells with potent antiviral and antibacterial functions protect the epithelial and mucosal surfaces of our bodies against infection with pathogens. The strong proinflammatory activities of T cells suggest requirement for expression of inhibitory molecules to restrain these memory T cells under steady state conditions. We previously identified the adhesion G protein-coupled receptor GPR56 as an inhibitory receptor of human cytotoxic lymphocytes that regulates their cytotoxic effector functions.

The Potential of Tissue-Resident Memory T Cells for Adoptive Immunotherapy against Cancer.

Tissue-resident memory T cells (T) comprise an important memory T cell subset that mediates local protection upon pathogen re-encounter. T populations preferentially localize at entry sites of pathogens, including epithelia of the skin, lungs and intestine, but have also been observed in secondary lymphoid tissue, brain, liver and kidney. More recently, memory T cells characterized as T have also been identified in tumors, including but not limited to melanoma, lung carcinoma, cervical carcinoma, gastric carcinoma and ovarian carcinoma.

Effector differentiation downstream of lineage commitment in ILC1s is driven by Hobit across tissues.

Innate lymphoid cells (ILCs) participate in tissue homeostasis, inflammation, and early immunity against infection. It is unclear how ILCs acquire effector function and whether these mechanisms differ between organs. Through multiplexed single-cell mRNA sequencing, we identified cKitCD127TCF-1 early differentiation stages of T-bet ILC1s.

Hobit identifies tissue-resident memory T cell precursors that are regulated by Eomes.

Tissue-resident memory CD8 T cells (T) constitute a noncirculating memory T cell subset that provides early protection against reinfection. However, how T arise from antigen-triggered T cells has remained unclear. Exploiting the T-restricted expression of Hobit, we used T reporter/deleter mice to study T differentiation.

T-cell memory in tissues.

Immunological memory equips our immune system to respond faster and more effectively against reinfections. This acquired immunity was originally attributed to long-lived, memory T and B cells with body wide access to peripheral and secondary lymphoid tissues. In recent years, it has been realized that both innate and adaptive immunity to a large degree depends on resident immune cells that act locally in barrier tissues including tissue-resident memory T cells (Trm).

Adenoviral vaccines promote protective tissue-resident memory T cell populations against cancer.

Background: Adenoviral vectors emerged as important platforms for cancer immunotherapy. Vaccination with adenoviral vectors is promising in this respect, however, their specific mechanisms of action are not fully understood. Here, we assessed the development and maintenance of vaccine-induced tumor-specific CD8 T cells elicited upon immunization with adenoviral vectors.

Area under Immunosurveillance: Dedicated Roles of Memory CD8 T-Cell Subsets.

Immunological memory, defined as the ability to respond in an enhanced manner upon secondary encounter with the same pathogen, can provide substantial protection against infectious disease. The improved protection is mediated in part by different populations of memory CD8 T cells that are retained after primary infection. Memory cells persist in the absence of pathogen-derived antigens and enable secondary CD8 T-cell responses with accelerated kinetics and of larger magnitude after reencounter with the same pathogen.

Circulating memory CD8 T cells are limited in forming CD103 tissue-resident memory T cells at mucosal sites after reinfection.

Tissue-resident memory CD8 T cells (T ) localize to barrier tissues and mediate local protection against reinvading pathogens. Circulating central memory (T ) and effector memory CD8 T cells (T ) also contribute to tissue recall responses, but their potential to form mucosal T remains unclear. Here, we employed adoptive transfer and lymphocytic choriomeningitis virus reinfection models to specifically assess secondary responses of T and T at mucosal sites.