Generation of antigen specific cytotoxic T lymphocytes (CTL) directed against Class II molecules expressed by activated T cells

1985 ◽  
Vol 84 (1-2) ◽  
pp. 73-84 ◽  
Author(s):  
Karen S. Zier
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Class Ii ◽  
Activated T Cells

scholarly journals Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Alexandria C Wells ◽  
Keith A Daniels ◽  
Constance C Angelou ◽  
Eric Fagerberg ◽  
Amy S Burnside ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Activated T Cells ◽  
Cell Responses

The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naive phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor-mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc and Eomesodermin. Ultimately, we have identified a novel let-7-mediated mechanism, which acts as a molecular brake controlling the magnitude of CD8 T cell responses.

Requirements for lysis of activated T cells by class-II-restricted cytolytic T-lymphocytes

1992 ◽  
Vol 35 (1) ◽  
pp. 50-59 ◽  
Author(s):  
Assia Eljaafari ◽  
Isabelle Dorval ◽  
Dominique Zeliszewski ◽  
Sylvie Le Gac ◽  
Ghislaine Sterkers
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Class Ii ◽  
Cytolytic T Lymphocytes ◽  
Activated T Cells

scholarly journals Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I-restricted cytotoxic T lymphocytes.

1987 ◽  
Vol 165 (6) ◽  
pp. 1508-1523 ◽  
Author(s):  
J Bastin ◽  
J Rothbard ◽  
J Davey ◽  
I Jones ◽  
A Townsend
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Infected Cell ◽  
Cytotoxic T Lymphocytes ◽  
Synthetic Peptides ◽  
Class Ii ◽  
Cytotoxicity Assay ◽  
Class I ◽  
Class I Mhc

The conserved epitopes of influenza nucleoprotein (NP) recognized by class I MHC-restricted CTL from CBA (H-2k) and C57BL/10 (H-2b) mice have been defined in vitro with synthetic peptides 50-63 and 365-379, respectively. Two Db-restricted clones were described that recognize different epitopes on peptide 365-379. Finally, the recognition of complete NP was shown to be approximately 200-fold less efficient than peptide in the cytotoxicity assay. These phenomena are closely related to results with class II-restricted T cells and they strengthen the hypothesis that influenza proteins are degraded in the infected cell before recognition by class I-restricted CTL.

scholarly journals Transcriptional reprogramming of mature CD4+ helper T cells generates distinct MHC class II–restricted cytotoxic T lymphocytes

2013 ◽  
Vol 14 (3) ◽  
pp. 281-289 ◽  
Author(s):  
Daniel Mucida ◽  
Mohammad Mushtaq Husain ◽  
Sawako Muroi ◽  
Femke van Wijk ◽  
Ryo Shinnakasu ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mhc Class Ii ◽  
Cytotoxic T Lymphocytes ◽  
Class Ii ◽  
Helper T Cells ◽  
Transcriptional Reprogramming

scholarly journals Presentation of peptides by cultured monocytes or activated T cells allows specific priming of human cytotoxic T lymphocytes in vitro

1995 ◽  
Vol 7 (11) ◽  
pp. 1741-1752 ◽  
Author(s):  
Maria Cristina Gagliardi ◽  
Guido De Petrillo ◽  
Simonetta Salemi ◽  
Laura Boffa ◽  
Maria Grazia Longobardi ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Activated T Cells ◽  
Specific Priming

Effect of MUC5B mutation on prognosis by enhancing the infiltration and antitumor immunity of cytotoxic T lymphocytes in the endometrial cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18105-e18105
Author(s):  
Hong Zheng ◽  
Wei Duan ◽  
Qun Zhao ◽  
Chengcheng Li ◽  
Guoqiang Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Endometrial Cancer ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Molecular Subtypes ◽  
The Cancer Genome Atlas ◽  
Research Network ◽  
Sequencing Data ◽  
Activated T Cells ◽  
Endometrial Cancers

e18105 Background: Endometrial cancers have been categorized into four genomic classes by The Cancer Genome Atlas Research Network (TCGA) with comprehensive genomic analysis. However, TCGA molecular subtypes are hard to utilize in clinic as the expensive cost and a simply version of POLE, TP53 genes cannot fully differentiate the four subtypes. Therefore, more convenient and reliable biomarkers need to be identified for clinical practice. Methods: Whole-exome sequencing and RNA sequencing data for 515 patients with endometrial carcinomas were downloaded from TCGA. Associations between MUC5B mutation and survival and RNA expression were analyzed. Results: MUC5B mutation was associated with a prolonged disease specific survival (DSS) (HR, 0.47; 95% CI, 0.28-0.79; P < 0.05), progression-free survival (PFS) (HR, 0.31; 95% CI, 0.17-0.56; P < 0.001) and overall survival (OS) (HR, 0.29; 95% CI, 0.14-0.60; P = 0.001) in endometrial cancers. MUC5B mutation was significantly associated with patients' age at diagnosis (P = 0.027) and histological type (P < 0.001) and grade (P < 0.001). In the multivariable cox proportional hazards regression model including FIGO 2008, histology types, tumor grade, tp53, pole and TCGA molecular subtypes, the association between MUC5B mutation and PFS was still significant (HR, 0.40; 95% CI, 0.20-0.81; P = 0.011), indicating the MUC5B mutation is an independent prognostic factor for PFS. Moreover, MUC5B mutation have a tendency for a favorable OS (HR, 0.52; 95% CI, 0.23-1.22; P = 0.13). Patients harboring MUC5B have a higher tumor mutation burden (TMB). An analysis of immune signature revealed that MUC5B mutation was involved with the increase of genes related to activated T cells, immune cytolytic activity, and IFN-γ release. These results have further been confirmed by GSEA. Moreover, an increased level of cytotoxic T lymphocytes infiltration was observed in the patients with MUC5B mutations. Conclusions: MUC5B mutation was related with a favorable prognosis through increasing T cells signature. Identification of MUC5B mutation by genomic profiling provides a potentially novel and convenient approach for endometrial cancer patients to predict the prognosis.

scholarly journals Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dehua Lu ◽  
Yanpu Wang ◽  
Ting Zhang ◽  
Feng Wang ◽  
Kui Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Solid Tumors ◽  
Cytotoxic T Lymphocytes ◽  
Pet Imaging ◽  
Stage Migration ◽  
Cell Transfer ◽  
Tumor Infiltration ◽  
Antitumor Effects

Abstract Background Adoptive T cell transfer-based immunotherapy yields unsatisfactory results in the treatment of solid tumors, partially owing to limited tumor infiltration and the immunosuppressive microenvironment in solid tumors. Therefore, strategies for the noninvasive tracking of adoptive T cells are critical for monitoring tumor infiltration and for guiding the development of novel combination therapies. Methods We developed a radiolabeling method for cytotoxic T lymphocytes (CTLs) that comprises metabolically labeling the cell surface glycans with azidosugars and then covalently conjugating them with 64Cu-1,4,7-triazacyclononanetriacetic acid-dibenzo-cyclooctyne (64Cu-NOTA-DBCO) using bioorthogonal chemistry. 64Cu-labeled control-CTLs and ovalbumin-specific CTLs (OVA-CTLs) were tracked using positron emission tomography (PET) in B16-OVA tumor-bearing mice. We also investigated the effects of focal adhesion kinase (FAK) inhibition on the antitumor efficacy of OVA-CTLs using a poly(lactic-co-glycolic) acid (PLGA)-encapsulated nanodrug (PLGA-FAKi). Results CTLs can be stably radiolabeled with 64Cu with a minimal effect on cell viability. PET imaging of 64Cu-OVA-CTLs enables noninvasive mapping of their in vivo behavior. Moreover, 64Cu-OVA-CTLs PET imaging revealed that PLGA-FAKi induced a significant increase in OVA-CTL infiltration into tumors, suggesting the potential for a combined therapy comprising OVA-CTLs and PLGA-FAKi. Further combination therapy studies confirmed that the PLGA-FAKi nanodrug markedly improved the antitumor effects of adoptive OVA-CTLs transfer by multiple mechanisms. Conclusion These findings demonstrated that metabolic radiolabeling followed by PET imaging can be used to sensitively profile the early-stage migration and tumor-targeting efficiency of adoptive T cells in vivo. This strategy presents opportunities for predicting the efficacy of cell-based adoptive therapies and for guiding combination regimens. Graphic Abstract

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