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Cytotoxic T cell

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https://www.readbyqxmd.com/read/28087665/nkg2d-promotes-b1a-cell-development-and-protection-against-bacterial-infection
#1
Maja Lenartić, Vedrana Jelenčić, Biljana Zafirova, Mateja Ožanič, Valentina Marečić, Slaven Jurković, Veronika Sexl, Marina Šantić, Felix M Wensveen, Bojan Polić
NKG2D is a potent activating receptor that is expressed on cytotoxic immune cells such as CD8 T and NK cells, where it promotes cytotoxicity after binding stress ligands on infected or transformed cells. On NK cell precursors NKG2D modulates proliferation and maturation. Previously, we observed that NKG2D deficiency affects peripheral B cell numbers. In this study, we show that NKG2D regulates B1a cell development and function. We find that mice deficient for NKG2D have a strong reduction of B1a cell numbers...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087292/loss-of-cd28-within-cd4-t-cell-subsets-from-cervical-cancer-patients-is-accompanied-by-the-acquisition-of-intracellular-perforin-and-is-further-enhanced-by-nkg2d-expression
#2
Marta Escarra-Senmarti, Miriam Ruth Bueno-Topete, Luis Felipe Jave-Suarez, Eduardo Gomez-Bañuelos, Jorge Gutierrez-Franco, Natali Vega-Magaña, Adriana Aguilar-Lemarroy, Ana Laura Pereira-Suarez, Jesse Haramati, Susana Del Toro-Arreola
CD28 is well characterized as an essential co-stimulatory receptor critical for activation, proliferation and survival processes in CD4(+) T cells. Populations of CD4(+)CD28(null) T cells, with apparently contradictory physiological roles, have recently been reported, along with the co-expression of the NK activating receptor NKG2D, in autoimmune diseases and chronic viral inflammation. Paradoxically, studies in cancer suggest that an expanded CD4(+)NKG2D(+) population may be armed with immunosuppressive properties...
January 10, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28087047/rational-design-of-low-immunogenic-anti-cd25-recombinant-immunotoxin-for-t-cell-malignancies-by-elimination-of-t-cell-epitopes-in-pe38
#3
Ronit Mazor, Gilad Kaplan, Dong Park, Youjin Jang, Fred Lee, Robert Kreitman, Ira Pastan
LMB-2, is a potent recombinant immunotoxin (RIT) that is composed of scFv antibody that targets CD25 (Tac) and a toxin fragment (PE38). It is used to treat T cell leukemias and lymphomas. To make LMB-2 less immunogenic, we introduced a large deletion in domain II and six point mutations in domain III that were previously shown to reduce T cell activation in other RITs. We found that unlike other RITs, deletion of domain II from LMB-2 severely compromised its activity. Rather than deletion, we identified T cell epitopes in domain II and used alanine substitutions to identify point mutations that diminished those epitopes...
January 5, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28081504/the-expression-and-function-of-the-neonatal-fc-receptor-in-thyrocytes-of-hashimoto-s-thyroiditis
#4
Chenxu Zhao, Ying Gao, Lanlan Zhao, Yuan Li, Yang Zhang, Suxia Wang, Hong Zhang, Guizhi Lu, Xiaohui Guo
OBJECTIVE: Thyroglobulin (Tg) and thyroid peroxidase (TPO) antibodies (TgAb and TPOAb), which are primarily of the immunoglobulin G (IgG) class, can mediate antibody-dependent cell-mediated cytotoxicity in vitro. However, it is unclear whether any thyrocyte molecules can facilitate the transport and elimination of TgAb and TPOAb. The IgG transport receptor neonatal Fc receptor (FcRn) is a candidate mediator of these processes. In this study, we aimed to evaluate FcRn expression and function in normal and Hashimoto's thyroiditis (HT) thyrocytes...
January 9, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28081442/mapping-and-role-of-the-cd8-t-cell-response-during-primary-zika-virus-infection-in-mice
#5
Annie Elong Ngono, Edward A Vizcarra, William W Tang, Nicholas Sheets, Yunichel Joo, Kenneth Kim, Matthew J Gorman, Michael S Diamond, Sujan Shresta
CD8(+) T cells may play a dual role in protection against and pathogenesis of flaviviruses, including Zika virus (ZIKV). We evaluated the CD8(+) T cell response in ZIKV-infected LysMCre(+)IFNAR(fl/fl) C57BL/6 (H-2(b)) mice lacking the type I interferon receptor in a subset of myeloid cells. In total, 26 and 15 CD8(+) T cell-reactive peptides for ZIKV African (MR766) and Asian (FSS13025) lineage strains, respectively, were identified and validated. CD8(+) T cells from infected mice were polyfunctional and mediated cytotoxicity...
January 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28079009/emerging-roles-of-calreticulin-in-cancer-implications-for-therapy
#6
Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G Raj, Ashok Prasad, Christophe Len, Virinder S Parmar, Bilikere Dwarakanath
Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies...
January 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28078578/cd95-stimulation-with-cd95l-and-disc-analysis
#7
Matthieu Le Gallo, Patrick Legembre
CD95 and its ligand CD95L play a major role in immune surveillance and homeostasis. CD95L is expressed by activated T lymphocytes and NK cells to induce apoptosis in cancer and virus-infected cells. The goal of this chapter is to describe a method used to immunoprecipitate CD95 and analyze its associated protein complex in cells stimulated with a cytotoxic CD95L (i.e., Ig-CD95L).
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078577/production-of-the-non-apoptotic-metalloprotease-cleaved-cd95l-and-its-cytotoxic-recombinant-counterpart-designed-ig-cd95l
#8
Eléonore Lepvrier, Sophie Martin, Brigitte Collet
The ligand of CD95, CD95L (also known as FasL or CD178), is a type II transmembrane protein that belongs to the Tumor Necrosis factor (TNF) family (Fig. 1a). This membrane-bound cytokine is mainly expressed at the surface of activated T lymphocytes and natural killer cells, where it is used as an apoptotic factor to eliminate infected and transformed cells (Strasser et al., Immunity 30:180-192, 2009).
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28077684/targeting-aurora-kinase-a-and-jak2-prevents-gvhd-while-maintaining-treg-and-antitumor-ctl-function
#9
Brian C Betts, Anandharaman Veerapathran, Joseph Pidala, Hua Yang, Pedro Horna, Kelly Walton, Christopher L Cubitt, Steven Gunawan, Harshani R Lawrence, Nicholas J Lawrence, Said M Sebti, Claudio Anasetti
Graft-versus-host disease (GVHD) is a leading cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation. T cell costimulation by CD28 contributes to GVHD, but prevention is incomplete when targeting CD28, downstream mammalian target of rapamycin (mTOR), or Aurora A. Likewise, interleukin-6 (IL-6)-mediated Janus kinase 2 (JAK2) signaling promotes alloreactivity, yet JAK2 inhibition does not eliminate GVHD. We provide evidence that blocking Aurora A and JAK2 in human T cells is synergistic in vitro, prevents xenogeneic GVHD, and maintains antitumor responses by cytotoxic T lymphocytes (CTLs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077649/tcr-clonotype-specific-differences-in-inhibitory-activity-of-hiv-1-cytotoxic-t-cell-clones-is-not-mediated-by-tcr-alone
#10
Nina C Flerin, Huabiao Chen, Tynisha D Glover, Pedro A Lamothe, Jian Hua Zheng, Justin W Fang, Zaza M Ndhlovu, Evan W Newell, Mark M Davis, Bruce D Walker, Harris Goldstein
: Functional analysis of T cell responses in HIV-infected individuals has indicated that virus-specific CD8(+) T cells with superior antiviral efficacy are well represented in HIV-1 controllers but are rare or absent in HIV-1 progessors. To define the role of individual TCR clonotypes in differential antiviral CD8(+) T cell function, we performed detailed functional and mass cytometric cluster analysis of multiple CD8(+) T cell clones recognizing the identical HLA-B*2705-restricted HIV-1 epitope KK10 (KRWIILGLNK)...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077213/inhibition-of-dopamine-receptor-d3-signaling-in-dendritic-cells-increases-antigen-cross-presentation-to-cd8-t-cells-favoring-anti-tumor-immunity
#11
Claudio Figueroa, Felipe Gálvez-Cancino, Cesar Oyarce, Francisco Contreras, Carolina Prado, Catalina Valeria, Sebastián Cruz, Alvaro Lladser, Rodrigo Pacheco
Dendritic cells (DCs) display the unique ability for cross-presenting antigens to CD8(+) T-cells, promoting their differentiation into cytotoxic T-lymphocytes (CTLs), which play a pivotal role in anti-tumor immunity. Emerging evidence points to dopamine receptor D3 (D3R) as a key regulator of immunity. Accordingly, we studied how D3R regulates DCs function in anti-tumor immunity. The results show that D3R-deficiency in DCs enhanced expansion of CTLs in vivo and induced stronger anti-tumor immunity. Co-culture experiments indicated that D3R-inhibition in DCs potentiated antigen cross-presentation and CTLs activation...
January 2, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28077081/antigen-presenting-capacity-of-murine-splenic-myeloid-cells
#12
Ying-Ying Hey, Benjamin Quah, Helen C O'Neill
BACKGROUND: The spleen is an important site for hematopoiesis. It supports development of myeloid cells from bone marrow-derived precursors entering from blood. Myeloid subsets in spleen are not well characterised although dendritic cell (DC) subsets are clearly defined in terms of phenotype, development and functional role. Recently a novel dendritic-like cell type in spleen named 'L-DC' was distinguished from other known dendritic and myeloid cells by its distinct phenotype and developmental origin...
January 11, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28076903/slamf7-engagement-restores-defective-effector-cd8-t-cells-activity-in-response-to-foreign-antigens-in-systemic-lupus-erythematosus
#13
Denis Comte, Maria P Karampetsou, Nobuya Yoshida, Katalin Kis-Toth, Vasileios C Kyttaris, George C Tsokos
OBJECTIVE: Effector CD8+ T cell function is impaired in SLE and associated with compromised ability to fight infections. SLAMF7 engagement has been shown to enhance NK cell degranulation. Thus, we characterized the expression and function of SLAMF7 on CD8+ T cells subsets isolated from peripheral blood of SLE patients and healthy subjects. METHODS: CD8+ T cell subset distribution, SLAMF7 expression and cytolytic enzyme expression (perforin, GzmA, GzmB) were monitored on cells isolated from SLE patients and healthy controls by flow cytometry...
January 11, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28076376/increased-natural-killer-cell-activation-in-hiv-infected-immunologic-non-responders-correlates-with-cd4-t-cell-recovery-after-antiretroviral-therapy-and-viral-suppression
#14
Zhenwu Luo, Zhen Li, Lisa Martin, Zhiliang Hu, Hao Wu, Zhuang Wan, Michael Kilby, Sonya L Heath, Lei Huang, Wei Jiang
The role of natural killer (NK) cell function in HIV disease especially in the setting of long-term antiretroviral therapy (ART) and viral suppression is not fully understood. In the current study, we have investigated NK cell activation in healthy controls and aviremic ART-treated HIV+ subjects with different degrees of immune restoration. We performed a cross sectional study in 12 healthy controls and 24 aviremic ART-treated HIV-infected subjects including 13 HIV+ subjects with CD4+ T cells above 500 cells/μL defined as "immunologic responders" and 11 HIV+ subjects with CD4+ T cells below 350 cells/μL defined as "immunologic non-responders"...
2017: PloS One
https://www.readbyqxmd.com/read/28075524/topk-t-lak-cell-originated-protein-kinase-inhibitor-exhibits-growth-suppressive-effect-on-small-cell-lung-cancer
#15
Jae-Hyun Park, Hiroyuki Inoue, Taigo Kato, Makda Zewde, Takashi Miyamoto, Yo Matsuo, Ravi Salgia, Yusuke Nakamura
T-lymphokine-activated killer cell-originated protein kinase (TOPK) plays critical roles in cancer cell proliferation as well as maintenance of cancer stem cells (CSC). Small cell lung cancer (SCLC) has highly aggressive phenotype, reveals early spread to distant sites, and results in dismal prognosis with little effective treatment. In this study, we demonstrate that TOPK expression was highly upregulated in both SCLC cell lines and primary tumors. Similar to siRNA-mediated TOPK knockdown effects, treatment with a potent TOPK inhibitor, OTS514, effectively suppressed growth of SCLC cell lines (IC50 ; 0...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28075442/increased-expression-of-pd%C3%A2-l1-by-the-human-papillomavirus-16-e7-oncoprotein-inhibits-anticancer-immunity
#16
Chaoqi Liu, Jiao Lu, Huiqun Tian, Wei Du, Lin Zhao, Jing Feng, Ding Yuan, Zhiying Li
Cytotoxic T lymphocyte dysfunction is frequently associated with PD‑L1/PD‑1 pathway activation, and is a principal obstacle in cancer therapy. In the present study, the mechanisms underlying the human papillomavirus (HPV)‑induced evasion of cervical cancer cells to the host immune system via the programmed death ligand  1/programmed death 1 (PD‑L1/PD‑1) signaling pathway was investigated. A significant increase in the expression of the HPV16E7 viral protein and PD‑L1 in cervical tissues was observed when compared with normal cervical tissues...
January 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28075428/balanced-secretion-of-anti-cea-x-anti-cd3-diabody-chains-using-the-2a-self-cleaving-peptide-maximizes-diabody-assembly-and-tumor-specific-cytotoxicity
#17
K Mølgaard, M Compte, N Nuñez-Prado, S L Harwood, L Sanz, L Alvarez-Vallina
Adoptive transfer of genetically engineered human cells secreting bispecific T cell engagers has shown encouraging therapeutic effects in preclinical models of cancer. However, reducing the toxicity and improving the effectiveness of this emerging immunotherapeutic strategy will be critical to its successful application. We have demonstrated that for gene-based bispecific antibody strategies, two-chain diabodies have a better safety profile than single-chain tandem scFvs, because their reduced tendency to form aggregates reduces the risk of inducing antigen-independent T cell activation...
January 11, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28075416/phosphorylated-radix-cyathulae-officinalis-polysaccharides-act-as-adjuvant-via-promoting-dendritic-cell-maturation
#18
Haibo Feng, Sean P McDonough, Jing Fan, Shiping Yang, Xuelian Zhao, Yong Lu, Yun Gan, Xiao Yi, Yung-Fu Chang
The aim of this study was to investigate whether phosphorylated Radix Cyathulae officinalis Kuan polysaccharides (pRCPS) used as adjuvant with foot-and-mouth disease vaccine (FMDV) can stimulate specific humoral and cellular immune responses in ICR mice. The results demonstrated that pRCPS significantly up-regulated FMDV-specific IgG, IgG1, IgG2b and IgG2a antibody levels and splenocyte proliferation. pRCPS also promoted the killing activities of cytotoxic T lymphocytes (CTL) and natural killer cells (NK). In addition, pRCPS enhanced the expression levels of IL-2, IL-4, and IFN-γ in CD4⁺ T cells and the level of IFN-γ in CD8⁺ T cells...
January 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28074937/circulating-t-lymphocyte-subsets-cytokines-and-immune-checkpoint-inhibitors-in-patients-with-bipolar-ii-or-major-depression-a-preliminary-study
#19
Wei Wu, Ya-Li Zheng, Li-Ping Tian, Jian-Bo Lai, Chan-Chan Hu, Peng Zhang, Jing-Kai Chen, Jian-Bo Hu, Man-Li Huang, Ning Wei, Wei-Juan Xu, Wei-Hua Zhou, Shao-Jia Lu, Jing Lu, Hong-Li Qi, Dan-Dan Wang, Xiao-Yi Zhou, Jin-Feng Duan, Yi Xu, Shao-Hua Hu
This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28074529/epigenetic-mediated-immune-suppression-of-positive-co-stimulatory-molecules-in-chemoresistant-ovarian-cancer-cells
#20
Ercan Cacan
The immunological response against cancer is a critical balance between immune-activating and immune-suppressing mechanisms. Ovarian cancer creates a suppressive microenvironment to escape immune elimination; however, the molecular mechanisms are poorly understood, and it is unclear whether chemotherapeutic drugs exert an immunoreactive or immunosuppressive effect on the tumor microenvironment. 4-1BB ligand (4-1BBL/CD157) and OX-40 ligand (OX-40L/CD252) are important regulators of effector cytotoxic T-cells activity...
January 11, 2017: Cell Biology International
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