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https://www.readbyqxmd.com/read/29683891/il-21-increases-the-reactivity-of-allogeneic-human-v%C3%AE-9v%C3%AE-2-t-cells-against-primary-glioblastoma-tumors
#1
Noémie Joalland, Cynthia Chauvin, Lisa Oliver, François M Vallette, Claire Pecqueur, Ulrich Jarry, Emmanuel Scotet
Glioblastoma multiforme (GBM) remains the most frequent and deadliest primary brain tumor in adults despite aggressive treatments, because of the persistence of infiltrative and resistant tumor cells. Nonalloreactive human Vγ9Vδ2 T lymphocytes, the major peripheral γδ T-cell subset in adults, represent attractive effectors for designing immunotherapeutic strategies to track and eliminate brain tumor cells, with limited side effects. We analyzed the effects of ex vivo sensitizations of Vγ9Vδ2 T cells by IL-21, a modulating cytokine, on their cytolytic reactivity...
April 20, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29669928/cx3cr1-identifies-pd-1-therapy-responsive-cd8-t-cells-that-withstand-chemotherapy-during-cancer-chemoimmunotherapy
#2
Yiyi Yan, Siyu Cao, Xin Liu, Susan M Harrington, Wendy E Bindeman, Alex A Adjei, Jin Sung Jang, Jin Jen, Ying Li, Pritha Chanana, Aaron S Mansfield, Sean S Park, Svetomir N Markovic, Roxana S Dronca, Haidong Dong
Although immune checkpoint inhibitors have resulted in durable clinical benefits in a subset of patients with advanced cancer, some patients who did not respond to initial anti-PD-1 therapy have been found to benefit from the addition of salvage chemotherapy. However, the mechanism responsible for the successful chemoimmunotherapy is not completely understood. Here we show that a subset of circulating CD8+ T cells expressing the chemokine receptor CX3CR1 are able to withstand the toxicity of chemotherapy and are increased in patients with metastatic melanoma who responded to chemoimmunotherapy (paclitaxel and carboplatin plus PD-1 blockade)...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29668066/mait-cell-mediated-cytotoxicity-roles-in-host-defense-and-therapeutic-potentials-in-infectious-diseases-and-cancer
#3
REVIEW
Patrick T Rudak, Joshua Choi, S M Mansour Haeryfar
Mucosa-associated invariant T (MAIT) cells are unconventional, innate-like T lymphocytes that sense the presence of MHC-related protein 1 (MR1)-restricted ligands and select inflammatory cues. Consequently, they release potent immunomodulatory mediators, including IFN-γ, TNF-α, and/or IL-17. MAIT cells can also be viewed as killer cells. They display several NK cell-associated receptors, carry granules containing cytotoxic effector molecules, and swiftly upregulate perforin and granzymes upon activation. Accordingly, MAIT cells are capable of lysing MR1-expressing cells infected with a variety of pathogenic bacteria in in vitro settings and may also mount cytotoxic responses during microbial infections in vivo...
April 18, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29662120/an-early-history-of-t-cell-mediated-cytotoxicity
#4
REVIEW
Pierre Golstein, Gillian M Griffiths
After 60 years of intense fundamental research into T cell-mediated cytotoxicity, we have gained a detailed knowledge of the cells involved, specific recognition mechanisms and post-recognition perforin-granzyme-based and FAS-based molecular mechanisms. What could not be anticipated at the outset was how discovery of the mechanisms regulating the activation and function of cytotoxic T cells would lead to new developments in cancer immunotherapy. Given the profound recent interest in therapeutic manipulation of cytotoxic T cell responses, it is an opportune time to look back on the early history of the field...
April 16, 2018: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/29658580/norepinephrine-inhibits-the-cytotoxicity-of-nk92%C3%A2-mi-cells-via-the-%C3%AE-2%C3%A2-adrenoceptor-camp-pka-p%C3%A2-creb-signaling-pathway
#5
Zan Sun, Diandong Hou, Shuli Liu, Weixin Fu, Jiahui Wang, Zaifu Liang
Norepinephrine (NE) can regulate natural killer (NK) cell activity, but the mechanism remains unclear. In the present study the roles of adrenergic receptors (ARs) in inhibiting NK92‑MI cells‑mediated cytotoxicity by NE were investigated. To examine the effect of NE on NK92‑MI cytotoxicity, a lactate dehydrogenase‑release cytotoxicity assay was used to determine the cytotoxicity of NK92‑MI cells against K562 cells. To evaluate the possible function of the α, β1 and β2 AR in mediating NE‑induced effects, NK92‑MI cells were pre‑incubated with phenol‑amine, CGP20712A and ICI118551 prior to stimulation by NE...
April 12, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29657256/colonal-monomorphic-epitheliotropic-intestinal-t-cell-lymphoma-with-novel-phenotype-of-cytoplasmic-cd3-expression
#6
Yumi Aoyama, Hiroko Tsunemine, Yuriko Zushi, Hayato Maruoka, Yuta Goto, Taiichi Kodaka, Tomoo Itoh, Takayuki Takahashi
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a new clinical entity that was reclassified from enteropathy-associated T-cell lymphoma in the 2016 WHO classification. An 83-year-old man with fever and diarrhea was referred to our hospital because of free air in the abdominal cavity and wall thickening of the large intestine on CT. Colonofiberscopic examination revealed mucosal edema and multiple ulcers at the sigmoid colon, splenic flexure, and transverse colon. Histopathological examination of the mucosal biopsy specimen demonstrated dense infiltration of small lymphocytes with nuclear atypia, some of which exhibited intraepithelial invasion...
April 13, 2018: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/29625086/tr1-responses-are-elevated-in-asymptomatic-h-pylori-infected-individuals-and-are-functionally-impaired-in-h-pylori-gastric-cancer-patients
#7
Zongchang Song, Tongxia Zhang, Guang Li, Ying Tang, Yan Luo, Genhua Yu
Gastric cancer is one of the most lethal malignancies worldwide. Chronic Helicobacter pylori (H. pylori) infection can induce an inflammatory response that promotes atrophic gastritis, a preceding event to cancer development. The type 1 regulatory T (Tr1) cells have recently emerged as a critical participant in maintaining self-tolerance. In this study, we examined Tr1 cells in H. pylori infection and gastric cancer development. While H. pylori-uninfected (uninfected) subjects presented low Tr1 frequency in the peripheral blood, H...
April 3, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29619420/changes-in-natural-killer-cells-and-exhausted-memory-regulatory-t-cells-with-corticosteroid-therapy-in-acute-autoimmune-hepatitis
#8
Hannah C Jeffery, Manjit K Braitch, Chris Bagnall, James Hodson, Louisa E Jeffery, Rebecca E Wawman, Lin Lee Wong, Jane Birtwistle, Helen Bartlett, Ansgar W Lohse, Gideon M Hirschfield, Jessica Dyson, David Jones, Stefan G Hubscher, Paul Klenerman, David H Adams, Ye H Oo
Autoimmune hepatitis (AIH) is an immune-mediated liver disease currently treated by immunosuppressive medications with significant side effects. Thus, novel mechanistic treatments are greatly needed. We performed prospective deep immunophenotyping of blood immune cells in patients with acute AIH before and after corticosteroid therapy. Blood samples from 26 patients with acute AIH (United Kingdom-AIH Consortium) were phenotyped by flow cytometry at baseline and 4 months after starting corticosteroids. Pretreatment liver tissues were stained for forkhead box P3-positive (FOXP3POS ) regulatory T cells (Tregs), clusters of differentiation (CD)56POS natural killer (NK) cells, and chemokine (C-X-C motif) ligand 10...
April 2018: Hepatology communications
https://www.readbyqxmd.com/read/29610856/natural-killer-cell-inhibition-by-hla-e-molecules-on-induced-pluripotent-stem-cell-derived-retinal-pigment-epithelial-cells
#9
Sunao Sugita, Kenichi Makabe, Yuko Iwasaki, Shota Fujii, Masayo Takahashi
Purpose: To determine whether human induced pluripotent stem (iPS) cell-derived retinal pigment epithelial (RPE) cells (iPS-RPE) can suppress natural killer (NK) cell activation. Methods: iPS-RPE cells were cocultured with peripheral blood mononuclear cells (PBMCs) or purified NK cells from healthy donors after stimulation with cytokines. To confirm expression of NK cell-specific markers, flow cytometry and quantitative RT-PCR (qRT-PCR) were performed. NK cells (or PBMCs) cocultured with iPS-RPE cells were assessed for proliferation by Ki-67 expression with flow cytometry, and NK suppression by RPE cells was assessed for granzyme B production with ELISA...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29603342/indeterminate-pediatric-acute-liver-failure-is-uniquely-characterized-by-a-cd103-cd8-t-cell-infiltrate
#10
Catherine A Chapin, Thomas Burn, Tomas Meijome, Kathleen M Loomes, Hector Melin-Aldana, Portia A Kreiger, Peter F Whitington, Edward M Behrens, Estella M Alonso
The cause of pediatric acute liver failure (PALF) is unknown in up to 40% of cases. Evidence suggests aberrant immune system activation may play a role. We hypothesized indeterminate PALF cases would exhibit a unique pattern of hepatic inflammation. This was a retrospective and prospective study of PALF cases due to indeterminate (iPALF), autoimmune hepatitis (AIH), or known diagnosis (dPALF) etiology. Liver tissue sections were stained with immunohistochemical (IHC) markers for cytotoxic T-cells (CD8), perforin, and tissue resident memory T-cells (CD103), and scored as minimal, moderate, or dense...
March 30, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29602283/korean-mistletoe-lectin-enhances-natural-killer-cell-cytotoxicity-via-upregulation-of-perforin-expression
#11
Younghoon Kim, Inbo Kim, Choon-Ho Park, Jong Bae Kim
BACKGROUND: Natural killer (NK) cells are crucial components of the innate immune system, providing the first line of defense against pathogens. In a previous study, we demonstrated prophylactic activity of water extract of Korean mistletoe (Viscum album coloratum) on tumor metastasis. However, the leading compound from water extract of Korean mistletoe was not clearly addressed. OBJECTIVE: The purpose of this research was mainly focused on addressing the effect of Korean mistletoe lectin (KMLC) on NK cell cytotoxicity, and the ability of cytokine secretion as well as its signal transduction, mitogen-activated protein kinase (MAPK) pathway...
March 31, 2018: Asian Pacific Journal of Allergy and Immunology
https://www.readbyqxmd.com/read/29599780/bi-allelic-mutations-in-stxbp2-reveal-a-complementary-role-for-stxbp1-in-cytotoxic-lymphocyte-killing
#12
Jamie A Lopez, Tahereh Noori, Adrian Minson, Lu Li Jovanoska, Kevin Thia, Michael S Hildebrand, Hedieh Akhlaghi, Phillip K Darcy, Michael H Kershaw, Natasha J Brown, Andrew Grigg, Joseph A Trapani, Ilia Voskoboinik
The ability of cytotoxic lymphocytes (CL) to eliminate virus-infected or cancerous target cells through the granule exocytosis death pathway is critical to immune homeostasis. Congenital loss of CL function due to bi-allelic mutations in PRF1, UNC13D, STX11 , or STXBP2 leads to a potentially fatal immune dysregulation, familial haemophagocytic lymphohistiocytosis (FHL). This occurs due to the failure of CLs to release functional pore-forming protein perforin and, therefore, inability to kill the target cell...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29599759/emergence-of-cd4-and-cd8-polyfunctional-t-cell-responses-against-immunodominant-lytic-and-latent-ebv-antigens-in-children-with-primary-ebv-infection
#13
Janice K P Lam, K F Hui, Raymond J Ning, X Q Xu, K H Chan, Alan K S Chiang
Long term carriers were shown to generate robust polyfunctional T cell (PFC) responses against lytic and latent antigens of Epstein-Barr virus (EBV). However, the time of emergence of PFC responses against EBV antigens, pattern of immunodominance and difference between CD4+ and CD8+ T cell responses during various stages of EBV infection are not clearly understood. A longitudinal study was performed to assess the development of antigen-specific PFC responses in children diagnosed to have primary symptomatic (infectious mononucleosis [IM]) and asymptomatic (AS) EBV infection...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29592963/single-degranulations-in-nk-cells-can-mediate-target-cell-killing
#14
Lavesh A Gwalani, Jordan S Orange
NK cells are cytotoxic lymphocytes important in defense against viral infection and cancer. NK cells mediate cytotoxicity predominantly through directed secretion of lytic granules, which are specialized lysosome-related organelles, containing effector molecules such as perforin and granzymes. Although many requirements for lytic granule transport to, and secretion at, the NK cell lytic synapse are known, the minimum number of degranulation events required by an NK cell to kill its target is unknown. We performed high-resolution four-dimensional confocal microscopy of human NK-target cell conjugates to quantify NK cell degranulation (using a degranulation indicator, LAMP-1-pHluorin) as well as target cell death...
March 28, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29589006/pretreatment-with-dihydroquercetin-a-dietary-flavonoid-protected-against-concanavalin-a-induced-immunological-hepatic-injury-in-mice-and-tnf-%C3%AE-actd-induced-apoptosis-in-hepg2-cells
#15
Jiajie Chen, Xu Sun, Tingting Xia, Qiqi Mao, Liang Zhong
We have previously demonstrated the hepatoprotective effect of dihydroquercetin (DHQ) against concanavalin A (Con A)-induced immunological hepatic injury in mice. In this study, we investigated the immunoregulatory effects of DHQ on Con A-induced liver injury in mice. DHQ administration significantly decreased the serum levels of alanine transaminase and aspartate transaminase, effectively prevented liver damage, and increased the survival rate of Con A-treated mice. Immunohistochemistry examination revealed that supplementation with DHQ obviously reduced infiltration of CD4+ and CD8+ T cells in the injured liver tissues...
March 28, 2018: Food & Function
https://www.readbyqxmd.com/read/29582167/amniotic-membrane-extract-differentially-regulates-human-peripheral-blood-t-cell-subsets-monocyte-subpopulations-and-myeloid-dendritic-cells
#16
Paula Laranjeira, Marta Duque, Martin Vojtek, Maria J Inácio, Isabel Silva, Ana C Mamede, Mafalda Laranjo, Susana Pedreiro, Maria J Carvalho, Paulo Moura, Ana M Abrantes, Cláudio J Maia, Pedro Domingues, Rosário Domingues, António Martinho, Maria F Botelho, Hélder Trindade, Artur Paiva
The discovery of the immunoregulatory potential of human amniotic membrane (hAM) propelled several studies focusing on its application for the treatment of immunological disorders. However, there is little information regarding the effects of hAM on distinct activation and differentiation stages of immune cells. Here, we aim to investigate the effect of human amniotic membrane extract (hAME) on the pattern of cytokine production by T cells, monocytes and myeloid dendritic cells (mDCs). For this purpose, peripheral blood mononuclear cells (PBMCs) from eight healthy individuals were stimulated in vitro in the presence or absence of hAME...
March 26, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29577371/role-of-t-bet-the-master-regulator-of-th1-cells-in-the-cytotoxicity-of-murine-cd4-t-cells
#17
Koji Eshima, Kana Misawa, Chihiro Ohashi, Kazuya Iwabuchi
Although CD4+ T cells are generally regarded as helper T cells, some activated CD4+ T cells exert cytotoxicity. Since CD4+ cytotoxic T lymphocytes (CTLs) often secrete IFN-γ, CTL activity among CD4+ T cells may be attributable to Th1 cells, where a T-box family molecule, T-bet serves as the "master regulator". However, although the essential contribution of T-bet to the expression of IFN-γ has been well-documented, it remains unclear if T-bet is involved in CD4+ T cell-mediated cytotoxicity. In this study, in order to investigate the ability of T-bet to confer cytolytic activity on CD4+ T cells, we introduced the T-bet gene into non-cytocidal CD4+ T cell lines and analyzed their cytolytic function...
March 25, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29562445/-expressions-and-clinical-significance-of-gas1-il-1rap-and-prf1-in-patients-with-alk-positive-anaplastic-large-cell-lymphoma
#18
Y Jiang, D Cao, C G Xu
Objective: To investigate the expressions of growth arrest-specific protein (GAS1), IL-1 receptor accessory protein (IL-1RAP) and perforin (PRF1) in patients with anaplastic lymphoma kinase positive, anaplastic large cell lymphoma (ALK+ ALCL) and their relationships with clinical significances and the prognoses of ALK+ ALCL. Methods: Twenty-six formalin-fixed paraffin-embedded (FFPE) samples of ALK+ ALCL patients who were diagnosed from January 2011 to September 2016 were collected. Twelve FFPE samples of patients with ALK+ ALCL, 13 FFPE samples of patients with peripheral T cell lymphoma (not otherwise specified) (PTCL-NOS) and 8 FFPE samples of patients with angioimmunoblastic T-cell lymphoma (AITL) were used as control groups...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29561433/primary-testicular-natural-killer-t-cell-lymphoma-a-care-case-report-and-review-of-literature
#19
Wan-Lin Zhang, Shuang Ma, Rachel Jug, Fan Li, Endi Wang, Huan-Yu Zhao, Hong-Tao Xu, Lin Cai, Cheng-Qian Yu, Shuai Shen, Lian-He Yang
RATIONALE: Primary testicular natural killer (NK)/T-cell lymphoma is an extremely rare and highly aggressive lymphoid malignancy. At present, only 20 cases have been reported. PATIENT CONCERNS: A 32-year-old Chinese man complained of discomfort and swelling of his right testicle for 3 months. Physical examination revealed a 10 × 10 × 9.5 cm mass on the right side of the scrotum area. DIAGNOSES: Pathologic evaluation showed effacement of normal testicular parenchymal architecture by small-to-medium-sized lymphoid cells with irregular nuclear profiles, and immunohistochemical studies positively expressed CD2, CD56, cytoplasmic CD3, granzyme B, perforin, and TIA-1...
March 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29552184/%C3%AE-%C3%AE-t-cell-mediated-individualized-immunotherapy-for-hepatocellular-carcinoma-considering-clinicopathological-characteristics-and-immunosuppressive-factors
#20
Wei Tian, Jun Ma, Ruyi Shi, Chongren Ren, Jiefeng He, Haoliang Zhao
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. γδ T cells have been revealed to be promising candidates for immunotherapy in patients with HCC. However, the use of these cells in clinical practice has been demonstrated to be challenging. In the present study, γδ T cells isolated from the peripheral blood of patients with HCC (n=83) and healthy donors (n=15) were characterized. Flow cytometry was used to analyze the proportion, phenotype, tumor-killing capacity and cytokine secretion of regulatory T cells (Tregs) and γδ T17 cells in peripheral blood samples prior to and following amplification...
April 2018: Oncology Letters
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