Engagement of the costimulatory molecule ICOS in tissues promotes establishment of CD8+ tissue-resident memory T cells

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Enzymatic Activity of HPGD in Treg Cells Suppresses Tconv Cells to Maintain Adipose Tissue Homeostasis and Prevent Metabolic Dysfunction

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The Emergence and Functional Fitness of Memory CD4+ T Cells Require the Transcription Factor Thpok

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Gut tissue-resident memory T cells in coeliac disease

This mini-review describes observations of the 1990ies with culturing of gluten-specific and astrovirus-specific CD4⁺ T cells from duodenal biopsies from subjects who presumably had a long time between the exposure to gluten or astrovirus antigens and the sampling of the biopsy. In these studies, it was also observed that antigen-specific CD4⁺ T cells migrated out of the gut biopsies during overnight culture. The findings are suggestive of memory T cells in tissue which are resident, but which also can be mobilised on antigen stimulation. Of note, these findings were made years before the term tissue-resident memory T cells was invoked. Since that time, many observations have accumulated on these gut T cells, particularly the gluten-specific T cells, and we have insight into the turnover of CD4⁺ T cells in the gut lamina propria. These data make it evident that human antigen-specific CD4⁺ T cells that can be cultured from gut biopsies indeed are bone fide tissue-resident memory T cells.     

Intratumoral Tcf1+PD-1+CD8+ T Cells with Stem-like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy

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KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages,and Convey Enhanced Protective Immunity

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A Mutation in the Transcription Factor Foxp3 Drives T Helper 2 Effector Function in Regulatory T Cells

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Competition for Active TGFβ Cytokine Allows for Selective Retention of Antigen-Specific Tissue- Resident Memory T Cells in the Epidermal Niche

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T cell and dendritic cell interactions in lymphoid organs: More than just being in the right place at the right time

The initiation of T lymphocyte responses within secondary lymphoid organs involves interactions with different subsets of dendritic cells (DCs). Recent studies have revealed the complexity of microanatomical organization within lymphoid organs. Exactly how T cells and DCs locate each other and the type of cellular interactions required for optimal priming of effector and memory T cell responses are beginning to be unraveled. Here we review advances in our understanding of how T cell priming is choreographed during infections, highlight the importance of cell positioning in this process and discuss how a spectrum of cellular interactions shapes T cell activation and differentiation.     

Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19

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Proteomic Analyses of Human Regulatory T Cells Reveal Adaptations in Signaling Pathways that Protect Cellular Identity

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Interleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1β-Producing Myeloid Cells that Promote Pathogenic T Cells

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Anti-CD44 Monoclonal Antibody Inhibits Heart Transplant Rejection Mediated by Alloantigen-primed CD4+ Memory T Cells in Nude Mice

Donor-reactive CD4⁺memory T cells threaten the survival of transplanted organs. In this study, we used anti-CD44 monoclonal antibody (mAb) to inhibit adoptively transferred B6-reactive CD4⁺memory Tcells (BALB/c origin) and to induce tolerance of B6 hearts in nude mice. The median survival time (MST) of the grafts was 6 days in the isotype group, and more than 100 days in the group treated with 8 doses of anti-CD44 at four-day intervals. Histological analysis revealed that the mean rejection level was Grade 3 in the isotype group, and Grade 0 or 1 in the multi-dose anti-CD44 treatment group. Compared with the isotype group, the multiply treated anti-CD44 group had significantly decreased IL-2 and IFN-γ expressions, while IL-10 and TGF-β were increased in the serum and the graft. Foxp3 in the graft was also increased. These data demonstrate that alloreactive CD4⁺ memory T cells mediate the destruction of allografts, and the adhesion molecule CD44 plays an important role in this course. Anti-CD44 mAb may promote the reduction of CD4⁺memory T cells and the production of regulatory T cells (Tregs). Furthermore, Tregs are maintained at a certain level while suppressing cellular immunity and inducing the grafts long-term survival in transplant recipients.     

Heterogenous Populations of Tissue-Resident CD8+ T Cells Are Generated in Response to Infection and Malignancy

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Tissue‐resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer

Tissue‐resident memory T (T_RM) cells are CD8⁺ T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in T_RM cells and correlate it with their functional potential. Fifty‐three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in T_RM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in‐vitro stimulation were used to evaluate T_RM cell phenotypes. We discovered that tumour T_RM cells have low DNA methylation in the PRF1 locus (32·9% methylation), which corresponds to increased numbers of perforin‐expressing T_RM cells. Surprisingly, programmed cell death 1 (PD‐1) expression is high in tumour T_RM cells, suggesting exhaustion. Following interleukin‐15 and T cell receptor stimulation, perforin and T‐bet expressions are enhanced, indicating that T_RM cells from tumours are not terminally exhausted. Moreover, a high number of T_RM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, T_RM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies T_RM cells as potential new targets for cancer immunotherapy.     

Human Fetal TNF-α-Cytokine-Producing CD4+ Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life

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