Результаты поиска

Increased Colonic Levels of CD8+ Cytotoxic T lymphocyte-Associated Mediators in Patients With Microscopic Colitis.

BACKGROUND: For unidentified reasons, possibly due to increased immune surveillance, patients with collagenous colitis (CC) and lymphocytic … , chitinase 3-like 1, pentraxin-3, Fas, and IL-33 were higher in UC than MC. Increases in 4-1BB and perforin in MC compared to controls were lower than in UC. Levels of gp130 and IL-6Rα were decreased in MC but increased in UC compared to controls. CONCLUSIONS: Microscopic colitis patients exhibit increased levels of several analytes, including some assoc …

Dynamics and immunological signature of γδ T cells following antiretroviral therapy initiation in acute HIV-1 Infection.

Early antiretroviral therapy (ART) is essential for controlling HIV-1 replication and boosting immune function. γδ T cells, as a vital compo … ells, particularly within the PD-1+ subset, remains elevated post-ART. We also noted a reduction in perforin secretion in PD-1+ Vδ1 and Vδ2 T cells of people living with HIV (PLWH). Furthermore, Vδ1 T cells were identified as the predominant regulatory T cells, with TGF-β production and co-expression of CD127 and CXCR4, negatively correlated with CD8+ T ce …

Flow cytometry immune profiling of recurrent and newly diagnosed growth hormone secreting pituitary neuroendocrine tumors: comparison of two clinical cases.

Early detection of aggressive pituitary neuroendocrine tumors (PitNETs) remains challenging due to the absence of reliable markers that can … xicity of CD8 + T cells and NK-cells. In the aggressive TIME the number of effector cells producing perforin and granzyme B-both independently and simultaneously was significantly lower. The proportion of CD3-CD20- NK cells and CD3-CD56 + NK cells was low after the first recurrence but increased sharply after six months. The ratio of monocyte subpopulation …

Inhibiting mTORC1 pathway by rapamycin restores the balance of CD8+ T cell subsets and reduces CD8+ T cell-mediated platelet destruction in immune thrombocytopenia.

BACKGROUND: CD8+ T cells contribute to platelet destruction in immune thrombocytopenia (ITP). Rapamycin, a mechanistic target of rapamycin complex 1 (mTORC1) inhibitor, has demonstrated efficacy in relapsed/refractory ITP. However, its impact on CD8+ T cells in ITP remains unexplored. METHODS: Gene expression profiles from GSE43177 dataset were analyzed using gene set enrichment analysis (GSEA). Activation of the mTORC1 pathway and CD8+ T cell subsets was evaluated using flow cytometry. CD8+ T cell cytotoxicity was assessed by measuring perforin, granzyme B expression and platelet apoptosis. …

Dysfunctional Senescent Herpes Simplex Virus-Specific CD57+CD8+ T Cells Are Associated with Symptomatic Recurrent Ocular Herpes in Humans.

Herpes simplex virus (HSV)-specific CD8+ T cells protect mice from herpes infection and disease. However, the phenotype and function of HSV- … 28 on HSV-specific CD8+ T cells; and (v) decreased production of effector molecules (granzyme B and perforin) by HSV-specific CD8+ T cells. Our findings provide insights into the role of senescence in HSV-specific CD8+ T cells in susceptibility to recurrent herpes and have implications for T-cell-based immunotherapeutic strategies against recurrent herpes …

SLAMF7 promotes TCRαβ+ double negative T cell antitumor activity through enhancing glutamine metabolism.

BACKGROUND: TCRαβ+ double negative T cells (DNT) have recently gained attention for their antitumor activity. Adoptive DNT therapy has emerg … s, increasing ATP production, enhancing the expression of effector molecules such as granzyme B and perforin, and promoting antitumor activity of DNT against tumor cells independent of homotypic ligand-receptor interactions. Secondly, DNT showed superior antitumor cytotoxicity against SLAMF7-expressing tumor cells because SLAMF7-SLAMF7 interaction between …

Selective impact of zinc on human circulating CD56dim NK cells.

PURPOSE: Natural Killer (NK) cells are essential for recognizing aberrant and virus-infected cells. Adequate levels of the trace element zin … expression and NFKB mRNA was significantly decreased in zinc-supplemented conditions. In addition, perforin levels were sensitive to zinc deprivation. CONCLUSION: Extracellular zinc selectively activates CD56dim NK cells enhancing degranulation and IFNγ production. Zinc supplementation might be a useful tool for in vitro NK cell expansion protocols for f …

Механистические понимания и достижения биконкретной T-клетки, использующей антителную терапию в мультимиеломе.

Множественная миелома (ММ) — клональная порча неизмеримо дифференцированных плазменных клеток, характеризующаяся инфильтрацией костного мозга и чрезмерным производством моноклонных иммуноглобулинов, что приводит к повреждению конечной формы, например остеолитических повреждений костей. Несмотря на значительный терапевтический прогресс, достигнутый с протеаозными ингибиторами, иммуномодуляционными препаратами и anti-CD38 Моноклональные антитела, множественная миелома остаются неизлечимыми, а результаты для трехклассных пациентов-восстановителей остаются мрачными, при этом медиана выживаемости н

Совпадение в аннотации оригинала
Multiple myeloma (MM) is a clonal malignancy of terminally differentiated plasma cells characterized by bone marrow infiltration and excessi … (FcRH5), thereby forming an immune synapse that triggers T cell activation, cytokine secretion, and perforin-granzyme-mediated apoptosis of the targeted B cell. This review summarizes the molecular design, mechanism of action, and clinical development of TCEs in MM, encompassing early bi-specific T cell engagers (BiTE) constructs such as AMG 420 and next-g …

BCL-2 Inhibitor Regulates Number, Function, and Antitumor Immunity of T Cells by Influencing Glycolysis in AML.

BCL-2 is one of the key genes in the mitochondrial apoptotic pathway, and BCL-2 inhibitor Venetoclax (VEN) is the preferred targeted drug fo … ry function and activation status of T cells in AML, which mainly manifested in promoting IFN-γ and Perforin and Granzyme B secretion, upregulating PD-1 expression, promoting T cell activation, and increasing the proportion of memory T cells. Finally, it was also observed that VEN could enhance T cell-mediated antitumor immune responses in AML. Mechanistic …

Dyslipidemia Is Associated With Increased Natural Killer Cell Cytotoxicity and Autoimmunity in Women With Recurrent Pregnancy Losses.

CONTEXT: Dyslipidemia adversely affects female fertility; however, its relation with recurrent pregnancy loss (RPL) and its underlying mecha … ow density lipoprotein (oxLDL) enhanced the conjugation of NK cells with target cells and increased perforin secretion. NK cell cytotoxicities were significantly increased after pretreatment with 5 and 50 μg/mL oxLDL (P < .05 each). CONCLUSION: A significant proportion of women with RPL have dyslipidemia, and the risk of autoimmune and cellular immune abn …

Immunomodulatory effects of dental pulp stem cells on lymphocytes and monocytes from patients with rheumatoid arthritis.

OBJECTIVES: To investigate the immunomodulatory effects of dental pulp stem cells (DPSCs) on lymphocytes and monocytes from rheumatoid arthr … D3/CD28-activated lymphocytes; and BAFF, sFas-L, IL-1β, sIL-6RA, IL-9, IL-17A, IL-18, IL-23, M-CSF, perforin, TNFα in supernatants of LPS-activated monocytes. IL-6 and IP-10 levels increased in all experimental conditions, while IL-9 increased in ODN 2006- and CD3/CD28-stimulated lymphocyte cultures. DPSCs showed differential effects depending on the activ …

A Noncanonical CD56dimCD16dim/- NK Cell Subset Indicative of Prior Cytotoxic Activity Is Elevated in Patients with Autoantibody-Mediated Neurologic Diseases.

Neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein Ab disease, and autoimmune myasthenia gravis (MG) are au … l maintaining expression of characteristic NK markers CD56, CD94, and NKp44. Notably, expression of perforin and granzyme is reduced in comparison with CD56dimCD16hi NK cells. Moreover, they exhibit elevated trogocytosis capability, HLA-DR expression, and many chemokine receptors, including CCR7. In contrast with NMOSD and MG, myelin oligodendrocyte glycop …

CD2 expressing innate lymphoid and T cells are critical effectors of immunopathogenesis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disease with a poorly understood immunopathogenesis. Here, we rep … epithelialized tunnels and fibrotic regions of the hypodermis. Whereas NK cells (CD2+CD56dim) were perforin+, granzymes A+ and B+, and enriched adjacent to hyperplastic follicular epidermis and tunnels of HS showing presence of apoptotic cells. The cytokines IL-12, IL-15, and IL-18, which enhance NK cell maturation and function were significantly elevated …

Cancer Cell Small Molecule Secretome Induces the Immune Checkpoint NKG2A and Dysfunction of Human CD8+ T Cells.

PD-1 blockade has been approved for head and neck squamous cell carcinoma (HNSCC) patients. However, many HNSCC patients do not respond to t … in TCM reduced CD8+ T cell cytotoxicity as shown by lower production of cytokines, granzyme B, and perforin. Furthermore, TCM prevented CD8+ T cells from killing cancer cells in response to an anti-CD19/anti-CD3 bispecific T cell engager. Thus, a small secreted molecule from HNSCC cells can induce NKG2A expression and promote T cell dysfunction. Our findi …

Stevens-Johnson syndrome and toxic epidermal necrolysis: Updates in pathophysiology and management.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions characterized by extensive detachment of … n SJS/TEN lesions is caused by extensive apoptosis, primarily through the Fas-Fas ligand (FasL) and perforin/granzyme pathways. Our findings suggest that necroptosis, a form of programmed necrosis, also contributes to epidermal cell death. Annexin A1, released from monocytes, interacts with the formyl peptide receptor 1 to induce necroptosis. Several bioma …

Antigen-specific age-related memory CD8 T cells induce and track Alzheimer's-like neurodegeneration.

Cerebral (Aβ) plaque and (pTau) tangle deposition are hallmarks of Alzheimer's disease (AD), yet are insufficient to confer complete AD-like … gressive neurodegeneration with both gross and fine features of sporadic human AD. T cells required Perforin to initiate this pathophysiology, and IFNγ for most gene expression changes and progression to more widespread neurodegenerative disease. Analogous antigen-specific memory CD8 T cells were significantly elevated in the brains of human AD patients, a …

Differential effects of itacitinib, fedratinib, and ruxolitinib in mouse models of hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) comprises a severe hyperinflammatory phenotype driven by the overproduction of cytokines, many of w … ved survival and clinical scores in CpG-induced secondary HLH. Conversely, in primary HLH, in which perforin-deficient (Prf1-/-) mice are infected with lymphocytic choriomeningitis virus (LCMV), itacitinib, and fedratinib performed suboptimally. Ruxolitinib demonstrated excellent clinical efficacy in both HLH models. RNA-sequencing of splenocytes from LCMV …

Preclinical evaluation of chimeric antigen receptor T cells targeting the carcinoembryonic antigen as a potential immunotherapy for gallbladder cancer.

Gallbladder cancer (GBC) is commonly diagnosed at late stages when conventional treatments achieve only modest clinical benefit. Therefore, … IFN-γ and TNF-α. In addition, CD8+ CAR-T cells up-regulated the cytotoxic molecules granzyme B and perforin. Interestingly, CAR-T cell activation occurred even in the presence of PD-L1. Consistent with these results, CAR-T cells efficiently recognized GBC cell lines expressing CEA and PD-L1, but not a CEA-negative cell line. Furthermore, CAR-T cells exhib …

Human granzyme B binds Plasmodium falciparum Hsp70-x and mediates antiplasmodial activity in vitro.

Cell surface-bound human Hsp70 (hHsp70) sensitises tumour cells to the cytolytic attack of natural killer (NK) cells through the mediation o … in facilitating GrB uptake in malaria parasite-infected RBCs remains unknown, but hHsp70 enables a perforin-independent uptake of GrB into tumour cells. In the current study, we comparatively investigated the direct binding of GrB to either PfHsp70-x or hHsp70 in vitro. Using ELISA, slot blot assay and surface plasmon resonance (SPR) analysis, we demonstr …

Cytotoxic innate intraepithelial lymphocytes control early stages of Cryptosporidium infection.

BACKGROUND: Intraepithelial lymphocytes (IELs) are the first immune cells to contact and fight intestinal pathogens such as Cryptosporidium, … st likely T-cell-like innate IELs, provide a rapid protection against C. parvum infection through a perforin/granzymes-dependent mechanism. C. parvum infection. The infection may also increase the sensitivity of intestinal epithelial cells to the innate IEL-mediated cytotoxic attack by decreasing the expression of Serpin genes.