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https://www.readbyqxmd.com/read/27895776/establishment-of-specific-cytotoxic-t-lymphocyte-culture-system-and-its-inhibitory-effect-on-ovarian-cancer
#1
Mingxing Sui, Lihui Si, Tianmin Xu, Manhua Cui
The present study aimed to establish a novel method for efficiently inducing cytotoxic T lymphocytes (CTLs) in vitro, in order to develop an immune-based therapy for suppressing and killing ovarian cancer cells with a high safety and efficacy. Peripheral blood mononuclear cells (PBMCs) were stimulated with CpG oligodeoxynucleotide (CpGODN) and ginsenoside Rg1, which were united as an immune adjuvant, and human epidermal growth factor receptor 2 (HER2/neu) antigen peptide, in order to establish a specific CTL culture system in vitro...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27872100/regeneration-of-cd8%C3%AE-%C3%AE-t-cells-from-t-cell-derived-ipsc-imparts-potent-tumor-antigen-specific-cytotoxicity
#2
Takuya Maeda, Seiji Nagano, Hiroshi Ichise, Keisuke Kataoka, Daisuke Yamada, Seishi Ogawa, Haruhiko Koseki, Toshio Kitawaki, Norimitsu Kadowaki, Akifumi Takaori-Kondo, Kyoko Masuda, Hiroshi Kawamoto
Although adoptive transfer of cytotoxic T lymphocytes (CTL) offer a promising cancer therapeutic direction, the generation of antigen-specific CTL from patients has faced difficulty in efficient expansion in ex vivo culture. To resolve this issue, several groups have proposed that induced pluripotent stem cell technology be applied for the expansion of antigen-specific CTL, which retain expression of the same T-cell receptor as original CTL. However, in these previous studies, the regenerated CTL are mostly of the CD8αα(+) innate type and have less antigen-specific cytotoxic activity than primary CTL...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27853459/immunosenescence-related-transcriptomic-and-immunologic-changes-in-older-individuals-following-influenza-vaccination
#3
Richard B Kennedy, Inna G Ovsyannikova, Iana H Haralambieva, Ann L Oberg, Michael T Zimmermann, Diane E Grill, Gregory A Poland
The goal of annual influenza vaccination is to reduce mortality and morbidity associated with this disease through the generation of protective immune responses. The objective of the current study was to examine markers of immunosenescence and identify immunosenescence-related differences in gene expression, gene regulation, cytokine secretion, and immunologic changes in an older study population receiving seasonal influenza A/H1N1 vaccination. Surprisingly, prior studies in this cohort revealed weak correlations between immunosenescence markers and humoral immune response to vaccination...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27837106/cutting-edge-t-regulatory-cell-depletion-reactivates-latent-simian-immunodeficiency-virus-siv-in-controller-macaques-while-boosting-siv-specific-t-lymphocytes
#4
Tianyu He, Egidio Brocca-Cofano, Benjamin B Policicchio, Ranjit Sivanandham, Rajeev Gautam, Kevin D Raehtz, Cuiling Xu, Ivona Pandrea, Cristian Apetrei
T regulatory cells (Tregs) are critical in shaping the latent HIV/SIV reservoir, as they are preferentially infected, reverse CD4(+) T cell activation status, and suppress CTL responses. To reactivate latent virus and boost cell-mediated immune responses, we performed in vivo Treg depletion with Ontak (denileukin diftitox) in two SIVsab-infected controller macaques. Ontak induced significant (>75%) Treg depletion and major CD4(+) T cell activation, and only minimally depleted CD8(+) T cells. The overall ability of Tregs to control immune responses was significantly impaired despite their incomplete depletion, resulting in both reactivation of latent virus (virus rebound to 10(3) viral RNA copies/ml plasma in the absence of antiretroviral therapy) and a significant boost of SIV-specific CD8(+) T cell frequency, with rapid clearance of reactivated virus...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27806296/opposing-development-of-cytotoxic-and-follicular-helper-cd4%C3%A2-t-cells-controlled-by-the-tcf-1-bcl6-nexus
#5
Tiziano Donnarumma, George R Young, Julia Merkenschlager, Urszula Eksmond, Nadine Bongard, Stephen L Nutt, Claude Boyer, Ulf Dittmer, Vu Thuy Khanh Le-Trilling, Mirko Trilling, Wibke Bayer, George Kassiotis
CD4(+) T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8(+) T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4(+) T cells. However, the conditions that induce CD4(+) CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)(+) CD4(+) CTLs, which distinguishes them from other CD4(+) T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27780916/efficient-generation-of-antigen-specific-ctls-by-the-baff-activated-human-b-lymphocytes-as-apcs-a-novel-approach-for-immunotherapy
#6
Zhang Yiwen, Gao Shilin, Chen Yingshi, Su Lishi, Luo Baohong, Liu Chao, Li Linghua, Pan Ting, Zhang Hui
Efficient antigen presentation is indispensable for cytotoxic T lymphocyte (CTL)-mediated immunotherapy. B-lymphocytes propagated with CD40L have been developed as antigen-presenting cells (APCs), but this capacity needs further optimization. Here, we aimed to expand human B-lymphocytes on a large scale while maintaining their antigen-presenting ability by using both CD40L and B-cell activating factor (BAFF). The addition of BAFF enhanced the expansion efficiency and prolonged the culture time without causing apoptosis of the expanded B-cells...
October 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27769524/dynamic-acquisition-of-htlv-1-tax-protein-by-mononuclear-phagocytes-role-in-neurologic-disease
#7
Eiji Matsuura, Yoshimi Enose-Akahata, Karen Yao, Unsong Oh, Yuetsu Tanaka, Hiroshi Takashima, Steven Jacobson
Pathology of HTLV-1 associated myelopathy/Tropical spastic paraparesis (HAM/TSP) is believed to be the result of "bystander damage" involving effector CD8 (+) T lymphocytes (CTLs) killing of virus infected cells. But the specific cellular events leading up to tissue injury are still unclear. Here, we developed the Microscopy Imaging of Cytotoxic T lymphocyte assay with Fluorescence emission (MI-CaFé), an optimized visualization analysis to explore the interactions between CTLs and virus infected or viral antigen presenting target cells...
October 3, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27755110/early-evolution-of-hla-associated-escape-mutations-in-variable-gag-proteins-predicts-cd4-decline-in-hiv-1-subtype-c-infected-women
#8
Denis R Chopera, Roman Ntale, Nonkululeko Ndabambi, Nigel Garrett, Clive M Gray, David Matten, Quarraisha Abdool Karim, Salim Abdool Karim, Carolyn Williamson
OBJECTIVE: HIV-1 escape from cytotoxic T-lymphocytes (CTL) results in the accumulation of HLA-associated mutations in the viral genome. To understand the contribution of early escape to disease progression, this study investigated the evolution and pathogenic implications of CTL escape in a cohort followed from infection for five years. METHODS: Viral loads and CD4+ counts were monitored in 78 subtype C infected individuals from onset of infection until CD4+ decline to <350 cells/μl or five years post-infection...
October 14, 2016: AIDS
https://www.readbyqxmd.com/read/27722177/th17-cells-exhibit-antitumor-effects-in-mds-possibly-through-augmenting-functions-of-cd8-t-cells
#9
Jing Li, Lanzhu Yue, Huaquan Wang, Chunyan Liu, Hui Liu, Jinglian Tao, Weiwei Qi, Yihao Wang, Wei Zhang, Rong Fu, Zonghong Shao
Th17 cells are a newly found subset of distinct CD4+ Th effector cells' family and are found to play an important role in cancers. Myelodysplastic syndromes (MDS) are a common malignant hematological disease. Here, we showed that both the percentage and the function of Th17 cells were elevated in low-risk MDS while being decreased in high-risk MDS. Levels of upstream molecules of Th17 cells, IL-6 and IL-23, were higher in low-risk MDS but lower in high-risk MDS patients. The abnormal percentage of Th17 cells was closely related to clinical parameters including karyotype, morphologic blast percentage of bone marrow, peripheral absolute neutrophil count, and hemoglobin concentration...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27692091/marek-s-disease-virus-immunosuppression-alters-host-cellular-responses-and-immune-gene-expression-in-the-skin-of-infected-chickens
#10
Mohammad Heidari, Dan Wang, Phillip Delekta, Shuhong Sun
Marek's disease virus (MDV), a highly cell-associated lymphotropic α-herpesvirus, is the causative agent of Marek's disease (MD) in domestic chickens. MDV replicates in chicken lymphocytes and establishes a latent infection within CD4(+) T cells. The latently infected CD4(+) T cells carry the virus to visceral organs, peripheral nerves, and feather follicle epithelium (FFE). FFE is the only anatomical site where infectious enveloped cell-free virus particles are produced and disseminated into the environment...
November 1, 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27669687/an-effective-cytokine-adjuvant-vaccine-induces-autologous-t-cell-response-against-colon-cancer-in-an-animal-model
#11
Huanyu Ju, Wenjing Xing, Jinfeng Yang, Yang Zheng, Xiuzhi Jia, Benning Zhang, Huan Ren
BACKGROUND: Despite recent advances in early detection and improvements in chemotherapy for colon cancer, the patients still face poor prognosis of postoperative recurrence and metastasis, the median survival for patients with metastatic colorectal cancer is approximately 22-24 months. Some immunotherapeutic approaches had been attempted in colon cancer patients to significantly increase overall survival. A vaccine based approach has shown a novel direction for colon cancer prevention and therapy...
September 26, 2016: BMC Immunology
https://www.readbyqxmd.com/read/27639281/the-primary-immune-response-to-vaccinia-virus-vaccination-includes-cells-with-a-distinct-cytotoxic-effector-cd4-t-cell-phenotype
#12
C Mee Ling Munier, David van Bockel, Michelle Bailey, Susanna Ip, Yin Xu, Sheilajen Alcantara, Sue Min Liu, Gareth Denyer, Warren Kaplan, Kazuo Suzuki, Nathan Croft, Anthony Purcell, David Tscharke, David A Cooper, Stephen J Kent, John J Zaunders, Anthony D Kelleher
BACKGROUND: Smallpox was eradicated by a global program of inoculation with Vaccinia virus (VV). Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. METHODS: We undertook a detailed functional and genetic characterization of CD4 T-cells during acute VV-infection of humans...
October 17, 2016: Vaccine
https://www.readbyqxmd.com/read/27630237/monitoring-integration-over-time-supports-a-role-for-cytotoxic-t-lymphocytes-and-ongoing-replication-as-determinants-of-reservoir-size
#13
Marilia Rita Pinzone, Erin Graf, Lindsay Lynch, Brigit McLaughlin, Frederick M Hecht, Mark Connors, Stephen A Migueles, Wei-Ting Hwang, Giuseppe Nunnari, Una O'Doherty
: The dynamics of HIV reservoir accumulation off antiretroviral therapy (ART) is underexplored. Levels of integrated HIV DNA in peripheral blood mononuclear cells (PBMCs) were longitudinally monitored before and after antiviral therapy. HIV integration increased over time in both elite controllers (ECs; n = 8) and noncontrollers (NCs; n = 6) before ART, whereas integration remained stable in patients on ART (n = 4). The median annual fold change was higher in NCs than in ECs and negatively correlated with CD4/CD8 T-cell ratio...
December 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27622060/biphasic-function-of-tlr3-adjuvant-on-tumor-and-spleen-dendritic-cells-promotes-tumor-t-cell-infiltration-and-regression-in-a-vaccine-therapy
#14
Masahiro Azuma, Yohei Takeda, Hiroko Nakajima, Haruo Sugiyama, Takashi Ebihara, Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
Successful cancer immunotherapy necessitates T cell proliferation and infiltration into tumor without exhaustion, a process closely links optimal maturation of dendritic cells (DC), and adjuvant promotes this process as an essential prerequisite. Poly(I:C) has contributed to adjuvant immunotherapy that evokes an antitumor response through the Toll-loke receptor 3 (TLR3)/TICAM-1 pathway in DC. However, the mechanism whereby Poly(I:C) acts on DC for T cell proliferation and migration remains undetermined. Subcutaneous injection of Poly(I:C) regressed implant tumors (WT1-C1498 or OVA-EG7) in C57BL/6 mice, which coincided with tumor-infiltration of CD8(+) T cells...
August 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27588200/conditions-for-the-generation-of-cytotoxic-cd4-th-cells-that-enhance-cd8-ctl-mediated-tumor-regression
#15
Kunyu Li, Margaret Baird, Jianping Yang, Chris Jackson, Franca Ronchese, Sarah Young
Adoptive cell therapies (ACTs) using tumor-reactive T cells have shown clinical benefit and potential for cancer treatment. While the majority of the current ACT are focused on using CD8(+) cytotoxic T lymphocytes (CTL), others have shown that the presence of tumor-reactive CD4(+) T helper (Th) cells can greatly enhance the anti-tumor activity of CD8(+) CTL. However, difficulties in obtaining adequate numbers of CD4(+) Th cells through in vitro expansion can limit the application of CD4 Th cells in ACT. This study aims to optimize the culture conditions for mouse CD4 T cells to provide basic information for animal studies of ACT using CD4 T cells...
August 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27531823/dna-vaccine-with-discontinuous-t-cell-epitope-insertions-into-hsp65-scaffold-as-a-potential-means-to-improve-immunogenicity-of-multi-epitope-mycobacterium-tuberculosis-vaccine
#16
Manli Wu, Min Li, Yan Yue, Wei Xu
DNA-based vaccine is a promising candidate for immunization and induction of a T-cell-focused protective immune response against infectious pathogens such as Mycobacterium tuberculosis (M. tb). To induce multi-functional T response against multi-TB antigens, a multi-epitope DNA vaccine and a 'protein backbone grafting' design method is adopted to graft five discontinuous T-cell epitopes into HSP65 scaffold protein of M. tb for enhancement of epitope processing and immune presentation. A DNA plasmid with five T-cell epitopes derived from ESAT-6, Ag85B, MTB10...
September 2016: Microbiology and Immunology
https://www.readbyqxmd.com/read/27529554/histone-deacetylase-inhibitors-enhance-cd4-t-cell-susceptibility-to-nk-cell-killing-but-reduce-nk-cell-function
#17
Matthew Pace, James Williams, Ayako Kurioka, Andrew B Gerry, Bent Jakobsen, Paul Klenerman, Nneka Nwokolo, Julie Fox, Sarah Fidler, John Frater
In the search for a cure for HIV-1 infection, histone deacetylase inhibitors (HDACi) are being investigated as activators of latently infected CD4 T cells to promote their targeting by cytotoxic T-lymphocytes (CTL). However, HDACi may also inhibit CTL function, suggesting different immunotherapy approaches may need to be explored. Here, we study the impact of different HDACi on both Natural Killer (NK) and CTL targeting of HIV-1 infected cells. We found HDACi down-regulated HLA class I expression independently of HIV-1 Nef which, without significantly compromising CTL function, led to enhanced targeting by NK cells...
August 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27479183/hla-dpb1-mismatch-alleles-represent-powerful-leukemia-rejection-antigens-in-cd4-t-cell-immunotherapy-after-allogeneic-stem-cell-transplantation
#18
W Herr, Y Eichinger, J Beshay, A Bloetz, S Vatter, C Mirbeth, E Distler, U F Hartwig, S Thomas
Refractory or relapsed acute myeloid leukemia (AML) represents a frequent complication after allogeneic hematopoietic stem-cell transplantation (HSCT). We show herein that primary in vitro stimulation of CD45RA-selected CD4 T cells of stem-cell donors with 10/10 HLA-matched AML blasts results in expansion of cytolytic T-lymphocytes (CTL) that almost all recognize HLA-DPB1 mismatch alleles, which clinically occur in up to 80% of donor-patient pairs. Primary AML blasts were found to strongly express HLA-DPB1, whereas fibroblasts and keratinocytes used as surrogate target cells for graft-versus-host disease did express HLA-DPB1 only upon IFN-γ pre-treatment...
September 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27471635/biomarkers-of-immunogenic-stress-in-metastases-from-melanoma-patients-correlations-with-the-immune-infiltrate
#19
Sylvain Ladoire, Laura Senovilla, David Enot, François Ghiringhelli, Vichnou Poirier-Colame, Kariman Chaba, Gulsun Erdag, Jochen T Schaefer, Donna H Deacon, Laurence Zitvogel, Craig L Slingluff, Guido Kroemer
Melanoma is known to be under latent immunosurveillance. Here, we studied four biomarkers of immunogenic cell stress and death (microtubule-associated proteins 1A/1B light chain 3B (MAP-LC3B, best known as LC3B)-positive puncta in the cytoplasm as a sign of autophagy; presence of nuclear HMGB1; phosphorylation of eIF2α; increase in ploidy) in melanoma cells, in tissue microarrays (TMA) from metastases from 147 melanoma patients. These biomarkers of immunogenicity were correlated with the density of immune cells infiltrating the metastases and expressing CD3, CD4(+), CD8(+), CD20, CD45, CD56, CD138, CD163, DC-LAMP or FOXP3...
June 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27404943/improved-anti-treg-vaccination-targeting-foxp3-efficiently-decreases-regulatory-t-cells-in-mice
#20
Neda Mousavi Niri, Arash Memarnejadian, Younes Pilehvar-Soltanahmadi, Mohammadreza Agha Sadeghi, Mehdi Mahdavi, Nasim Kheshtchin, Samaneh Arab, Afshin Namdar, Farhad Jadidi, Nosratollah Zarghami, Jamshid Hajati
INTRODUCTION: The critical role of regulatory T (Treg) cells in dampening immune responses against tumor cells is apparent. Therefore, several methods have been introduced for eliminating Treg. Among them, inducing immune responses against Treg cells expressing Foxp3 transcription factor is a hopeful approach to decrease the frequency of Tregs. In current study, we used the chimeric FoxP3-Fc(IgG) fusion construct/protein to effectively stimulate the immune responses against Treg cells...
September 2016: Journal of Immunotherapy
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