Intraepithelial t cell

PURPOSE: We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients. PATIENTS AND METHODS: We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A)...

Intraepithelial lymphocytes (IELs) are T cells important for the maintenance of barrier integrity in the intestine. Colon IELs are significantly reduced in both MyD88-deficient mice and those lacking an intact microbiota, suggesting that MyD88-mediated detection of bacterial products is important for the recruitment and/or retention of these cells. Here, using conditionally deficient MyD88 mice, we show that myeloid cells are the key mediators of TCRαβ+ IEL recruitment to the colon. Upon exposure to luminal bacteria, myeloid cells produce sphingosine-1-phosphate (S1P) in a MyD88-dependent fashion...

Intraepithelial lymphocytes (IEL) expressing the γδ T cell receptor (TCR) survey the intestinal epithelium to limit the invasion of microbial pathogens. The production of type I interferon (IFN) is a central component of an antiviral immune response, yet how these pro-inflammatory cytokines contribute to γδ IEL effector function remains unclear. Based on the unique activation status of IELs, and their ability to bridge innate and adaptive immunity, we investigated the extent to which type I IFN signaling modulates γδ IEL function...

Non-responsive celiac disease (NRCD) is relatively common. It is generally attributed to persistent gluten exposure and resolves after correction of diet errors. However, other complications of CD and disorders clinically mimicking CD, need to be excluded. Novel therapies are being evaluated to facilitate mucosal recovery, which might benefit NRCD patients. Refractory CD (RCD) is rare and is currently divided into two types. The etiology of RCD type 1 (RCDI) is unclear, a possible switch to gluten-independent autoimmunity is suspected in some patients, while RCD type II (RCDII) represents a low-grade intraepithelial lymphoma...

Tumor-infiltrating lymphocytes (TILs) are associated with improved survival in patients with epithelial ovarian cancer. However, the evaluation of TILs has not been applied to routine clinical practice due to reproducibility issues. We developed two convolutional neural network models to detect TILs and to determine their spatial location in whole-slide images, and established a spatial assessment pipeline to objectively quantify intraepithelial and stromal TILs in patients with high-grade serous ovarian carcinoma...

OBJECTIVE: To evaluate predictors of recurrence and the risk of progression to carcinoma in patients with dVIN. METHODS: 36 self-identified White patients with dVIN from 2011 to 2022 were identified. Demographics, treatment and clinical course were abstracted. Histopathologic features and IHC stains were reviewed by 2 subspecialty pathologists. Standard statistical analyses were applied. RESULTS: Median cohort age was 70 years (range 39-91)...

BACKGROUND: Cervical cancer (CC) occupies a leading position in incidence among young women of reproductive age. In this connection, it is urgent to search for the most effective approaches to the diagnosis and treatment of this pathology. The purpose of the study was to evaluate the effectiveness of the PDT method using Cе6 with the control of the photobleaching using video and spectral fluorescence diagnostic methods, to develop the method of fluorescence-assisted systemic photodynamic therapy mediated with chlorin e6 for treatment CIN 3 and CIS...

The mammalian small intestine epithelium harbors a peculiar population of CD4+ CD8αα+ T cells that are derived from mature CD4+ T cells through reprogramming of lineage-specific transcription factors. CD4+ CD8αα+ T cells occupy a unique niche in T cell biology because they exhibit mixed phenotypes and functional characteristics of both CD4+ helper and CD8+ cytotoxic T cells. The molecular pathways driving their generation are not fully mapped. However, recent studies demonstrate the unique role of the commensal gut microbiota as well as distinct cytokine and chemokine requirements in the differentiation and survival of these cells...

Resident memory T (TRM ) 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 TRM expand in vivo after repeated antigenic stimulation indicate that these memory T cells are not terminally differentiated. This suggests an opportunity for in vitro TRM expansion to apply in an immunotherapy setting. However, it has also been shown that TRM may not maintain their identity and form circulating memory T cells after in vivo restimulation...

Resident epidermal T cells of murine skin, called dendritic epidermal T cells (DETCs), express an invariant γδ TCR that recognizes an unidentified self-ligand expressed on epidermal keratinocytes. Although their fetal thymic precursors are preprogrammed to produce IFN-γ, DETCs in the adult epidermis rapidly produce IL-13 but not IFN-γ early after activation. Here, we show that preprogrammed IFN-γ-producing DETC precursors differentiate into rapid IL-13 producers in the perinatal epidermis...

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a 5-year survival rate of 12.5%. PDAC predominantly arises from non-cystic pancreatic intraepithelial neoplasia (PanIN) and cystic intraductal papillary mucinous neoplasm (IPMN). We used multiplex immunofluorescence and computational imaging technology to characterize, map, and compare the immune microenvironments (IMEs) of PDAC and its precursor lesions. We demonstrate that the IME of IPMN was abundantly infiltrated with CD8+ T cells and PD-L1-positive antigen-presenting cells (APCs), whereas the IME of PanIN contained fewer CD8+ T cells and fewer PD-L1-positive APCs but elevated numbers of immunosuppressive regulatory T cells (Tregs)...

BACKGROUND: Dysregulated T lymphocyte response is thought to play a key role in chronic intestinal inflammation (CIE). OBJECTIVES: To evaluate the presence of changes in peripheral and intestinal T lymphocyte subsets and to describe potential immune and inflammatory biomarkers in dogs with CIE. ANIMALS: Sixteen healthy dogs and 26 dogs were diagnosed with CIE. METHODS: Prospective case-control study evaluating peripheral and intestinal T lymphocytes using flow cytometry and inflammatory markers obtained from complete blood cell counts...

BACKGROUND: Data suggest an association between positron emission tomography/CT (PET/CT) metabolic metrics and tumor microenvironment in several malignancies, and a potential role of PET/CT to monitor response to immunotherapy. OBJECTIVE: To evaluate the correlation between tumor loco-regional extension and tumor-infiltrating lymphocyte infiltration in locally advanced cervical cancer prior to concurrent chemo-radiotherapy.The secondary objective was to assess the association between tumor-infiltrating lymphocytes and PET/CT metabolic metrics...

BACKGROUND: Oral lichen planus (OLP) and oral epithelial dysplasia (OED) present diagnostic challenges due to clinical and histologic overlap. This study explores the immune microenvironment in OED, hypothesizing that immune signatures could aid in diagnostic differentiation and predict malignant transformation. METHODS: Tissue samples from OED and OLP cases were analyzed using immunofluorescence/immunohistochemistry (IF/IHC) for CD4, CD8, CD163/STAT1, and PD-1/PDL-1 expression...

Intraepithelial lymphocytes (IEL) reside in the epithelium at the interface between the contents of the intestinal lumen and the sterile environment of the lamina propria. Because of this strategic location, IEL play a crucial role in various immunological processes, ranging from pathogen control to tissue stability. In mice and humans, IEL exhibit high diversity, categorized into induced IEL (conventional CD4 and CD8αβ T cells) and natural IEL (TCRαβCD8αα, TCRγδ, and TCRneg IEL)...

Oral leukoplakia is the most frequent and potentially malignant lesion of the oral cavity. Although dysplasia grading remains the main factor for risk assessment, challenges persist in determining the exact risk of transformation, and the literature has focused on studying alternative biomarkers. The interaction between dysplastic epithelial cells and the microenvironment starts early, and the communication is mainly mediated by lymphocytes, inflammatory factors, fibroblasts, and the extracellular matrix, leading to dysplastic progression...

BACKGROUND: The breakdown of intestinal barrier integrity occurs after severe burn injury and is responsible for the subsequent reactions of inflammation and oxidative stress. A new protective strategy for the intestinal barrier is urgently needed due to the limitations of the traditional methods. Recently, the application of nanoparticles has become one of the promising therapies for many inflammation-related diseases or oxidative damage. Herein, we developed a new anti-inflammatory and antioxidant nanoparticle named luminol-conjugated cyclodextrin (LCD) and aimed to evaluate its protective effects in severe burn-induced intestinal injury...

BACKGROUND: Quantity and the spatial relationship of specific immune cell types can provide prognostic information in bladder cancer. OBJECTIVE: To characterize the spatial interplay and prognostic role of different immune cell subpopulations in bladder cancer. DESIGN, SETTING, AND PARTICIPANTS: A total of 2463 urothelial bladder carcinomas were immunostained with 21 antibodies using BLEACH&STAIN multiplex fluorescence immunohistochemistry in a tissue microarray format and analyzed using a framework of neuronal networks for an image analysis...

BACKGROUND: The increasing prevalence of food sensitivities has been attributed to changes in gut microenvironment; however, ubiquitous environmental triggers such as inorganic nanoparticles (NPs) used as food additives have not been thoroughly investigated. OBJECTIVES: We explored the impact of the NP-structured food-grade silicon dioxide (<mml:math xmlns:mml="https://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>f</mml:mi><mml:mi>g</mml:mi><mml:mtext>-</mml:mtext><mml:mrow><mml:msub><mml:mrow><mml:mi>SiO</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:math>) on intestinal immune response involved in oral tolerance (OT) induction and evaluated the consequences of oral chronic exposure to this food-additive using a mouse model of OT to ovalbumin (OVA) and on gluten immunopathology in mice expressing the celiac disease risk gene, HLA-DQ8...

Eosinophilic esophagitis (EoE) is an emerging chronic T helper type 2 (Th2)-associated, allergic, and immune-mediated disease, characterized histologically by eosinophil-predominant mucosal inflammation and clinically by esophageal dysfunction. Over the past years, the prevalence of EoE has dramatically increased globally. Until recently, most studies of EoE focused on using human biopsies, which are also used for diagnostic purposes, or esophageal epithelial cell lines, which led to major advances in the understanding of EoE...