keyword
https://read.qxmd.com/read/38515134/ctls-heterogeneity-and-plasticity-implications-for-cancer-immunotherapy
#1
REVIEW
Shengkun Peng, Anqi Lin, Aimin Jiang, Cangang Zhang, Jian Zhang, Quan Cheng, Peng Luo, Yifeng Bai
Cytotoxic T lymphocytes (CTLs) play critical antitumor roles, encompassing diverse subsets including CD4+, NK, and γδ T cells beyond conventional CD8+ CTLs. However, definitive CTLs biomarkers remain elusive, as cytotoxicity-molecule expression does not necessarily confer cytotoxic capacity. CTLs differentiation involves transcriptional regulation by factors such as T-bet and Blimp-1, although epigenetic regulation of CTLs is less clear. CTLs promote tumor killing through cytotoxic granules and death receptor pathways, but may also stimulate tumorigenesis in some contexts...
March 21, 2024: Molecular Cancer
https://read.qxmd.com/read/38499993/terminally-differentiated-cytotoxic-cd4-t-cells-were-clonally-expanded-in-the-brain-lesion-of-radiation-induced-brain-injury
#2
JOURNAL ARTICLE
Xueying Ma, You Zuo, Xia Hu, Sitai Chen, Ke Zhong, Ruiqi Xue, Shushu Gui, Kejia Liu, Shaojian Li, Xiaoqiu Zhu, Jingwen Yang, Zhenhong Deng, Xiaolu Liu, Yongteng Xu, Sheng Liu, Zhongshan Shi, Meijuan Zhou, Yamei Tang
BACKGROUND: Accumulating evidence supports the involvement of adaptive immunity in the development of radiation-induced brain injury (RIBI). Our previous work has emphasized the cytotoxic function of CD8+ T cells in RIBI. In this study, we aimed to investigate the presence and potential roles of cytotoxic CD4+ T cells (CD4+ CTLs) in RIBI to gain a more comprehensive understanding of adaptive immunity in this context. MAIN TEXT: Utilizing single-cell RNA sequencing (scRNA-seq), we analyzed 3934 CD4+ T cells from the brain lesions of four RIBI patients and identified six subclusters within this population...
March 2024: CNS Neuroscience & Therapeutics
https://read.qxmd.com/read/38423478/single-cell-landscape-of-functionally-cured-chronic-hepatitis-b-patients-reveals-activation-of-innate-and-altered-cd4-ctl-driven-adaptive-immunity
#3
JOURNAL ARTICLE
Balakrishnan Chakrapani Narmada, Atefeh Khakpoor, Niranjan Shirgaonkar, Sriram Narayanan, Pauline Poh Kim Aw, Malay Singh, Kok Haur Ong, Collins Oduor Owino, Jane Wei Ting Ng, Hui Chuing Yew, Nu Soibah Binte Mohamed Nasir, Veonice Bijin Au, Reina Sng, Nivashini Kaliaperumal, Htet Htet Toe Wai Khine, Francesca Casuscelli di Tocco, Otsuka Masayuki, Shamita Naikar, Hui Xin Ng, Su Li Chia, Cindy Xin Yi Seah, Myra Hj Alnawaz, Chris Lee Yoon Wai, Amy Yuh Ling Tay, Mangat Kamarjit Singh, Valerie Chew, Weimiao Yu, John Edward Connolly, Giridharan Periyasamy, Marie-Laure Plissonnier, Massimo Levrero, Seng Gee Lim, Ramanuj DasGupta
BACKGROUND & AIMS: Hepatitis B surface antigen (HBsAg) loss or functional cure (FC), is considered the desirable therapeutic outcome for chronic hepatitis B (CHB) patients. However, the immune-pathological biomarkers and underlying mechanisms remain unclear. In this study we comprehensively interrogate disease-associated cell states (DACS) identified within intra-hepatic tissue and matched PBMCs from either CHB or FC patients, at the resolution of single cells, to provide novel insights into putative mechanisms underlying FC...
February 27, 2024: Journal of Hepatology
https://read.qxmd.com/read/38412963/nfil3-contributes-to-cytotoxic-t-lymphocyte-mediated-killing
#4
JOURNAL ARTICLE
Tiphaine Douanne, Katharina Strege, Martin Del Castillo Velasco-Herrera, Adam M Rochussen, David J Adams, Gillian M Griffiths
Cytotoxic T lymphocytes (CTLs) are key effectors of the adaptive immune system that recognize and eliminate virally infected and cancerous cells. In naive CD8+ T cells, T-cell receptor (TCR) engagement drives a number of transcriptional, translational and proliferation changes over the course of hours and days leading to differentiation into CTLs. To gain a better insight into this mechanism, we compared the transcriptional profiles of naive CD8+ T cells to those of activated CTLs. To find new regulators of CTL function, we performed a selective clustered regularly interspaced short palindromic repeats (CRISPR) screen on upregulated genes and identified nuclear factor IL-3 (NFIL3) as a potential regulator of cytotoxicity...
February 2024: Open Biology
https://read.qxmd.com/read/38396108/characterization-of-human-cd4-eomes-gzmk-t-cell-subsets-unveils-an-uncoupling-of-suppressive-functions-from-il-10-producing-capacities
#5
JOURNAL ARTICLE
Nadia Pulvirenti, Ylenia Silvetri, Francesca Clemente, Roberto Bosotti, Elena Carelli, Giorgia Moschetti, Paola Gruarin, Chiara Vasco, Maria Cristina Crosti, Maria Lucia Sarnicola, Luca Valenti, Daniele Prati, Sergio Abrignani, Jens Geginat
Human CD4+ EOMES+ T cells are heterogeneous and contain Th1-cells, Tr1-cells, and CD4+ CTL. Tr1- cells and non-classical EOMES+ Th1-cells displayed, respectively, anti- and pro-inflammatory cytokine profiles, but both expressed granzyme-K, produced IFN-γ, and suppressed T-cell proliferation. Diffusion map suggested a progressive CD4+ T-cell differentiation from naïve to cytotoxic cells and identified EOMES+ Th1-cells as putative Tr1-cell precursors (pre-Tr1).
February 23, 2024: European Journal of Immunology
https://read.qxmd.com/read/38383773/cd4-t-cells-produce-ifn-i-to-license-cdc1s-for-induction-of-cytotoxic-t-cell-activity-in-human-tumors
#6
JOURNAL ARTICLE
Xin Lei, Daniël C de Groot, Marij J P Welters, Tom de Wit, Ellen Schrama, Hans van Eenennaam, Saskia J Santegoets, Timo Oosenbrug, Annemarthe van der Veen, Joris L Vos, Charlotte L Zuur, Noel F C C de Miranda, Heinz Jacobs, Sjoerd H van der Burg, Jannie Borst, Yanling Xiao
CD4+ T cells can "help" or "license" conventional type 1 dendritic cells (cDC1s) to induce CD8+ cytotoxic T lymphocyte (CTL) anticancer responses, as proven in mouse models. We recently identified cDC1s with a transcriptomic imprint of CD4+ T-cell help, specifically in T-cell-infiltrated human cancers, and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy. Here, we delineate the mechanism of cDC1 licensing by CD4+ T cells in humans. Activated CD4+ T cells produce IFNβ via the STING pathway, which promotes MHC-I antigen (cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses...
February 21, 2024: Cellular & Molecular Immunology
https://read.qxmd.com/read/38363226/cytotoxic-programming-of-cd4-t-cells-is-regulated-by-opposing-actions-of-the-related-transcription-factors-eos-and-aiolos
#7
JOURNAL ARTICLE
Devin M Jones, Jasmine A Tuazon, Kaitlin A Read, Melissa R Leonard, Srijana Pokhrel, Bharath K Sreekumar, Robert T Warren, Jacob S Yount, Patrick L Collins, Kenneth J Oestreich
In contrast to the "helper" activities of most CD4+ T effector subsets, CD4+ cytotoxic T lymphocytes (CD4-CTLs) perform functions normally associated with CD8+ T and NK cells. Specifically, CD4-CTLs secrete cytotoxic molecules and directly target and kill compromised cells in an MHC class II-restricted fashion. The functions of these cells have been described in diverse immunological contexts, including their ability to provide protection during antiviral and antitumor responses, as well as being implicated in autoimmunity...
February 16, 2024: Journal of Immunology
https://read.qxmd.com/read/38303079/abrogation-and-homeostatic-restoration-of-ige-responses-by-a-universal-ige-allergy-ctl-vaccine-the-three-signal-self-non-self-self-s-ns-s-theory
#8
JOURNAL ARTICLE
Swey-Shen Chen, Hailan Zhang
Natural IgE cytotoxic peptides (nECPs), which are derived from the constant domain of the heavy chain of human IgE producing B cells via endoplasmic reticulum (ER) stress, are decorated onto MHC class 1a molecules (MHCIa) as unique biomarkers for CTL (cytotoxic T lymphocyte)-mediated immune surveillance. Human IgE exhibits only one isotype and lacks polymorphisms; IgE is pivotal in mediating diverse, allergen-specific allergies. Therefore, by disrupting self-IgE tolerance via costimulation, the CTLs induced by nECPs can serve as universal allergy vaccines (UAVs) in humans to dampen IgE production mediated by diverse allergen-specific IgE-secreting B cells and plasma cells expressing surface nECP-MHCIa as targets...
February 1, 2024: Immunology
https://read.qxmd.com/read/38282832/use-of-rna-seq-to-identify-genes-encoding-cytokines-and-chemokines-activated-following-uptake-and-processing-a-candidate-peptide-vaccine-developed-against-mycobacterium-avium-subsp-paratuberculosis
#9
JOURNAL ARTICLE
Michelle Athena Decourcey, William Charles Davis, Cleverson de Souza
Analysis of the primary and recall responses to a membrane molecule (MMP), encoded by MAP2121c demonstrated that tri-directional signaling between the antigen-presenting cell (APC), CD4 and CD8 is essential for eliciting a CD8 cytotoxic T cell (CTL) response against Mycobacterium avium subsp. paratuberculosis. As reported here, RNA-sequencing was used to initiate the characterization of the signaling pathways involved in eliciting the development of CD8 CTL, starting with the characterization of the activation status of genes in monocyte-derived macrophages (MoMΦ) following uptake and processing MMP for the presentation of antigenic epitopes to CD4 and CD8 T cells...
2024: Braz J Vet Med
https://read.qxmd.com/read/38263169/in-vivo-assembly-of-epitope-coated-biopolymer-particles-that-induce-anti-tumor-responses
#10
JOURNAL ARTICLE
Devi Jenika, Saranya Pounraj, David Wibowo, Leonhard M Flaxl, Bernd H A Rehm, Justine D Mintern
There is an unmet need for antigen delivery systems that elicit efficient T cell priming to prevent infectious diseases or for treatment of cancers. Here, we explored the immunogenic potential of biologically assembled biopolymer particles (BPs) that have been bioengineered to display the antigenic MHC I and MHC II epitopes of model antigen ovalbumin (OVA). Purified dendritic cells (DCs) captured BP-OVA and presented the associated antigenic epitopes to CD4+ T cells and CD8+ T cells. Vaccination with BP-OVA in the absence of adjuvant elicited antigen presentation to OVA-specific CD8+ and CD4+ T cells and cross-primed effective cytotoxic T lymphocyte (CTL) killers...
January 23, 2024: NPJ Vaccines
https://read.qxmd.com/read/38257808/hiv-expression-in-infected-t-cell-clones
#11
REVIEW
Jason W Rausch, Shadab Parvez, Sachi Pathak, Adam A Capoferri, Mary F Kearney
The principal barrier to an HIV-1 cure is the persistence of infected cells harboring replication-competent proviruses despite antiretroviral therapy (ART). HIV-1 transcriptional suppression, referred to as viral latency, is foremost among persistence determinants, as it allows infected cells to evade the cytopathic effects of virion production and killing by cytotoxic T lymphocytes (CTL) and other immune factors. HIV-1 persistence is also governed by cellular proliferation, an innate and essential capacity of CD4+ T cells that both sustains cell populations over time and enables a robust directed response to immunological threats...
January 11, 2024: Viruses
https://read.qxmd.com/read/38244740/exosome-co-delivery-of-a-sting-agonist-augments-immunogenicity-elicited-by-cvb3-vp1-vaccine-via-promoting-antigen-cross-presentation-of-cd8-dcs
#12
JOURNAL ARTICLE
Changwei Zhang, Qinghui Cao, Yuanyu Li, Juan Lu, Sidong Xiong, Yan Yue
The induction of a robust CD8+ T cell response is critical for the success of an antiviral vaccine. In this study, we incorporated a STING agonist (SA) 2'3'-cGAMP into a previously developed exosome-based CVB3 viral myocarditis vaccine (Exo-VP1) to enhance its ability to induce CD8+ T cell responses and immunoprotection. Our results showed that compared to free SA adjuvant, exosome-mediated co-delivery (ExoSA -VP1) significantly enhanced SA uptake by dendritic cells (DCs) and more potently stimulated DC maturation...
January 18, 2024: International Journal of Biological Macromolecules
https://read.qxmd.com/read/38128704/a-comprehensive-exploration-of-the-heterogeneity-of-immune-cells-in-han-and-zang-systemic-lupus-erythematosus-patients-via-single-cell-rna-sequencing
#13
JOURNAL ARTICLE
Yongzhuo Wu, Chongjun Weng, Yali Zhou, Qinghuan Zhu, Yingying Liu, Junjuan Zheng, Binbin Yang, Wenting Cao, Limei Yuan, Meng Yang, Danqi Deng
UNLABELLED: Systemic Lupus Erythematosus (SLE) is an autoimmune sickness with unclear pathogenesis. The goal of this research was to reveal the heterogeneity of immune cells in SLE patients of Han and Zang nationality by single-cell RNA sequencing (scRNA-seq) and bioinformatics profiling. METHODS: A total of 94,102 peripheral blood mononuclear cells (PBMCs) from six volunteers with SLE (3 Zang, 3 Han) and six healthy controls were first conducted through scRNA-seq analysis...
December 20, 2023: Genomics
https://read.qxmd.com/read/38102684/the-inter-link-of-ageing-cancer-and-immunity-findings-from-real-world-retrospective-study
#14
JOURNAL ARTICLE
Xiaomin Fu, Peng Qin, Fanghui Li, Huifang Zhu, Hongqin You, Yong Zhang, Benling Xu, Tiepeng Li, Fang Zhang, Lu Han, Lingdi Zhao, Baozhen Ma, Zibing Wang, Quanli Gao
BACKGROUND: Although the concept of declined immune function associated with cancer has been accepted extensively, real-world clinical studies focusing on analysis of the peripheral blood immune changes underlying ageing, immunity and cancer are scarce. METHODS: In this case-control study, we retrospectively analysed 1375 cancer patients and enrolled 275 age and gender matched healthy individuals. Flow cytometry was conducted to assess the immune changes. Further analysis was examined by SPSS 17...
December 15, 2023: Immunity & Ageing: I & A
https://read.qxmd.com/read/38082101/clinical-characteristics-of-hepatitis-associated-aplastic-anemia-in-children
#15
JOURNAL ARTICLE
Lingling Fu, Jialu Zhang, Ruixin Wang, Bixi Yang, Hongmin Li, Hui Chen, Jie Ma
To understand the current situation of hepatitis-related aplastic anemia (HAAA) in children, we analyzed the patients with HAAA admitted to our hospital in the past 5 years to understand the disease characteristics and prognosis. The clinical data of patients with HAAA admitted to our hospital from February 2017 to May 2022 were retrospectively analyzed. A total of 81 patients with HAAA, 56 males and 25 females. The median onset age was 5.9 years. The median time from hepatitis to occurrence of hemocytopenia was 30 days, and the median follow-up time was 2...
February 2024: Annals of Hematology
https://read.qxmd.com/read/38077321/expansion-of-cd4-cytotoxic-t-lymphocytes-with-specific-gene-expression-patterns-may-contribute-to-suppression-of-tumor-immunity-in-oral-squamous-cell-carcinoma-single-cell-analysis-and-in-vitro-experiments
#16
JOURNAL ARTICLE
Hu Chen, Junsei Sameshima, Shiho Yokomizo, Tomoki Sueyoshi, Haruki Nagano, Yuka Miyahara, Taiki Sakamoto, Shinsuke Fujii, Tamotsu Kiyoshima, Thomas Guy, Seiji Nakamura, Masafumi Moriyama, Naoki Kaneko, Shintaro Kawano
BACKGROUND: Cancer immunotherapy targeting CD8+ T cells has made remarkable progress, even for oral squamous cell carcinoma (OSCC), a heterogeneous epithelial tumor without a substantial increase in the overall survival rate over the past decade. However, the therapeutic effects remain limited due to therapy resistance. Thus, a more comprehensive understanding of the roles of CD4+ T cells and B cells is crucial for more robust development of cancer immunotherapy. METHODS: In this study, we examined immune responses and effector functions of CD4+ T cells, CD8+ T cells and B cells infiltrating in OSCC lesions using single-cell RNA sequencing analysis, T cell receptor (TCR) and B cell receptor (BCR) repertoire sequencing analysis, and multi-color immunofluorescence staining...
2023: Frontiers in Immunology
https://read.qxmd.com/read/38029261/protective-immunity-induced-by-dna-vaccine-containing-tg-gra35-tg-gra42-and-tg-gra43-against-toxoplasma-gondii-infection-in-kunming-mice
#17
JOURNAL ARTICLE
Youbo Shi, Jianbing Li, Weili Yang, Jia Chen
BACKGROUND: Toxoplasma gondii can cause congenital infection and abortion in humans and warm-blooded animals. T. gondii dense granule proteins, GRA35, GRA42, and GRA43, play a critical role in the establishment of chronic infection. However, their potential to induce protective immunity against T. gondii infection remains unexplored. OBJECTIVE: This study aimed to test the efficacy of a DNA vaccine encompassing GRA35, GRA42, and GRA43 in inducing protective immunity against the highly virulent T...
2023: Frontiers in Cellular and Infection Microbiology
https://read.qxmd.com/read/37965314/cytotoxic-cd4-t-cells-in-chronic-viral-infections-and-cancer
#18
REVIEW
Anna Malyshkina, Alicia Brüggemann, Annette Paschen, Ulf Dittmer
CD4+ T cells play an important role in immune responses against pathogens and cancer cells. Although their main task is to provide help to other effector immune cells, a growing number of infections and cancer entities have been described in which CD4+ T cells exhibit direct effector functions against infected or transformed cells. The most important cell type in this context are cytotoxic CD4+ T cells (CD4+ CTL). In infectious diseases anti-viral CD4+ CTL are mainly found in chronic viral infections. Here, they often compensate for incomplete or exhausted CD8+ CTL responses...
2023: Frontiers in Immunology
https://read.qxmd.com/read/37928526/culture-filtrate-proteins-from-bcg-act-as-adjuvants-for-cytotoxic-t-lymphocyte-induction
#19
JOURNAL ARTICLE
Satoru Mizuno, Yasushi Chuma, Yukihiro Shibuya, Shigeo Horibata, Tomoe Baba, Emi Yokokawa, Kazuhiro Matsuo
Mycobacterium bovis bacilli Calmette-Guerin (BCG) is a licensed vaccine against tuberculosis. It requires attenuated live bacteria to be effective, possibly because actively secreted proteins play a critical role in inducing anti-tuberculosis immunity. BCG also functions as an effective adjuvant. Moreover, the effects of BCG components as adjuvants are not important as those of attenuated live BCG, which is used in cancer immunotherapy. However, the BCG secreted proteins have not been paid attention in anticancer immunity...
2023: Frontiers in Immunology
https://read.qxmd.com/read/37904962/abrogation-and-homeostatic-restoration-of-ige-responses-by-a-universal-ige-allergy-ctl-vaccine-the-three-signal-self-non-self-self-s-ns-s-model
#20
Swey-Shen Chen, Hailan Zhang
UNLABELLED: Natural IgE cytotoxic peptides (nECPs), which are derived from the constant domain of the heavy chain of human IgE producing B cells via endoplasmic reticulum (ER) stress, are decorated onto MHC class 1a molecules (MHCIa) as unique biomarkers for CTL (cytotoxic T lymphocyte)-mediated immune surveillance. Human IgE exhibits only one isotype and lacks polymorphisms; IgE is pivotal in mediating diverse, allergen-specific allergies. Therefore, by disrupting self-IgE tolerance via costimulation, the cytotoxic T lymphocytes (CTLs) induced by nECPs can serve as universal allergy vaccines (UAVs) in humans to dampen IgE production mediated by diverse allergen-specific IgE- secreting B cells and plasma cells expressing surface nECP-MHCIa as targets...
October 17, 2023: bioRxiv
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