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https://www.readbyqxmd.com/read/28611767/natural-killer-defective-maturation-is-associated-with-adverse-clinical-outcome-in-patients-with-acute-myeloid-leukemia
#1
Anne-Sophie Chretien, Cyril Fauriat, Florence Orlanducci, Claire Galseran, Jerome Rey, Gaelle Bouvier Borg, Emmanuel Gautherot, Samuel Granjeaud, Jean-François Hamel-Broza, Clemence Demerle, Norbert Ifrah, Catherine Lacombe, Pascale Cornillet-Lefebvre, Jacques Delaunay, Antoine Toubert, Emilie Gregori, Herve Luche, Marie Malissen, Christine Arnoulet, Jacques A Nunes, Norbert Vey, Daniel Olive
Accumulating evidence highlights natural killer (NK) cell parameters as potential prognostic factors in cancer patients, which provides a strong rationale for developing therapeutic strategies aiming at restoring NK cell. However, reaching this point warrants better characterization of tumor-induced NK cell alterations. Our group recently reported heterogeneous NK maturation in acute myeloid leukemia (AML) patients. However, the clinical significance of such observations remained to be assessed on a larger cohort of patients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28588205/human-uterine-lymphocytes-acquire-a-more-experienced-and-tolerogenic-phenotype-during-pregnancy
#2
Dorien Feyaerts, Marilen Benner, Bram van Cranenbroek, Olivier W H van der Heijden, Irma Joosten, Renate G van der Molen
Pregnancy requires a delicate immune balance that nurtures the allogeneic fetus, while maintaining reactivity against pathogens. Despite increasing knowledge, data is lacking on the transition of pre-pregnancy endometrial lymphocytes to a pregnancy state. Here, we immunophenotyped lymphocytes from endometrium (MMC), term decidua parietalis (DPMC), and PBMC for direct comparison. We found that the immune cell composition of MMC and DPMC clearly differ from each other, with less NK-cells, and more NKT-cells and T-cells in DPMC...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28586095/cmv-drives-the-expansion-of-highly-functional-memory-t-cells-expressing-nk-cell-receptors-in-renal-transplant-recipients
#3
Nandina Makwana, Bree Foley, Sonia Fernandez, Silvia Lee, Ashley Irish, Hanspeter Pircher, Patricia Price
Cytomegalovirus (CMV) is a common opportunistic infection encountered in renal transplant recipients (RTRs) and may be reactivated without symptoms at any time post-transplant. We describe how active and latent CMV affect T-cell subsets in RTRs who are stable on maintenance therapy. T-cell responses to CMV were assessed in RTRs (n = 54) >2 years post-transplant, and healthy controls (n = 38). Seven RTRs had CMV DNA detectable in plasma. CMV antibody and DNA aligned with increased proportions of CD8+ T cells and reduced CD4/CD8 ratios...
June 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28582858/alterations-in-the-peripheral-immune-system-in-dementia
#4
Mandy Busse, Enrico Michler, Franz von Hoff, Henrik Dobrowolny, Roland Hartig, Thomas Frodl, Stefan Busse
Alterations in the immune response that result in inflammation might play a role in the pathology of dementias. In order to analyze changes of the peripheral immune system associated with different types of dementias, we determined several innate and adaptive cell populations in whole blood using flow cytometry. We included patients with Alzheimer's disease (AD; n = 60), vascular dementia (VaD; n = 20), and frontotemporal dementia (FTD; n = 12) at the time point of diagnosis and 24 age-matched neuropsychiatric healthy persons...
May 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28574833/new-interleukin-15-superagonist-il-15sa-significantly-enhances-graft-versus-tumor-activity
#5
Cavan P Bailey, Tulin Budak-Alpdogan, Christopher T Sauter, Michelle M Panis, Cihangir Buyukgoz, Emily K Jeng, Hing C Wong, Neal Flomenberg, Onder Alpdogan
Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28572802/chimeric-antigen-receptor-engineered-nk-92-cells-an-off-the-shelf-cellular-therapeutic-for-targeted-elimination-of-cancer-cells-and-induction-of-protective-antitumor-immunity
#6
Congcong Zhang, Pranav Oberoi, Sarah Oelsner, Anja Waldmann, Aline Lindner, Torsten Tonn, Winfried S Wels
Significant progress has been made in recent years toward realizing the potential of natural killer (NK) cells for cancer immunotherapy. NK cells can respond rapidly to transformed and stressed cells and have the intrinsic potential to extravasate and reach their targets in almost all body tissues. In addition to donor-derived primary NK cells, also the established NK cell line NK-92 is being developed for adoptive immunotherapy, and general safety of infusion of irradiated NK-92 cells has been established in phase I clinical trials with clinical responses observed in some of the cancer patients treated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28557197/impaired-immune-function-in-children-and-adults-with-fanconi-anemia
#7
Kasiani C Myers, Sharon Sauter, Xue Zhang, Jacob J Bleesing, Stella M Davies, Susanne I Wells, Parinda A Mehta, Ashish Kumar, Daniel Marmer, Rebecca Marsh, Darron Brown, Melinda Butsch Kovacic
BACKGROUND: Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA. PROCEDURE: We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls...
May 30, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28520183/infected-malnourished-children-displayed-changes-in-early-activation-and-lymphocyte-subpopulations
#8
Oralia Nájera-Medina, Fernando Valencia-Chavarría, Consuelo Cortés-Bejar, Monika Palacios-Martínez, C Paulina Rodríguez-López, María Cristina González-Torres
AIM: Malnutrition and infections cause immunological changes in lymphocyte subpopulations and their functionality. We evaluated the activation capacity of lymphocytes and memory cells in 10 well nourished, seven well nourished infected and eight malnourished infected children before and after treatment. METHODS: All the children were patients in Mexico City and were less than three years of age. The expression of various cluster of differentiation (CD) cells were assessed by flow cytometry: CD45RA (naïve) and CD45RO (memory) antigens on CD4 lymphocytes and CD69 in all lymphocytes...
May 18, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/28498953/pathological-role-of-anti-cd4-antibodies-in-hiv-infected-immunologic-non-responders-under-viral-suppressive-antiretroviral-therapy
#9
Zhenwu Luo, Zhen Li, Lisa Martin, Zhuang Wan, Eric G Meissner, Enrique Espinosa, Hao Wu, Xiaocong Yu, Pingfu Fu, Maria Anna Julia Westerink, J Michael Kilby, Jennifer Wu, Lei Huang, Sonya L Heath, Zihai Li, Wei Jiang
Increased mortality and morbidity occurs in human immunodeficiency virus (HIV)-infected patients who fail to increase CD4+ T cell counts despite achieving viral suppression with antiretroviral therapy (ART). Here we identified an underlying mechanism. Significantly elevated plasma levels of anti-CD4 IgGs were found in HIV+ immunologic non-responders (CD4+ T cell counts ≤ 350 cells/μl) compared to HIV+ immunologic responders (CD4+ T cell counts ≥ 500 cells/μl) and healthy controls. Higher plasma level of anti-CD4 IgG correlated with blunted CD4+ T cell recovery...
May 11, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28498568/reconstitution-of-immune-cell-populations-in-multiple-sclerosis-patients-after-autologous-stem-cell-transplantation
#10
REVIEW
F G Karnell, D Lin, S Motley, T Duhen, N Lim, D J Campbell, L A Turka, H T Maecker, K M Harris
Multiple sclerosis is an inflammatory T cell-mediated autoimmune disease. In a Phase II clinical trial, high-dose immunosuppressive therapy combined with autologous CD34(+) haematopoietic stem cell transplant resulted in 69·2% of subjects remaining disease-free without evidence of relapse, loss of neurological function or new magnetic resonance imaging (MRI) lesions to year 5 post-treatment. A combination of CyTOF mass cytometry and multi-parameter flow cytometry was used to explore the reconstitution kinetics of immune cell subsets in the periphery post-haematopoietic cell transplant (HSCT) and the impact of treatment on the phenotype of circulating T cells in this study population...
May 12, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28490677/dietary-human-milk-oligosaccharides-but-not-prebiotic-oligosaccharides-increase-circulating-natural-killer-cell-and-mesenteric-lymph-node-memory-t-cell-populations-in-noninfected-and-rotavirus-infected-neonatal-piglets
#11
Sarah S Comstock, Min Li, Mei Wang, Marcia H Monaco, Theresa B Kuhlenschmidt, Mark S Kuhlenschmidt, Sharon M Donovan
Background: Human milk oligosaccharides (HMOs) have antimicrobial and immunomodulatory actions. It has previously been reported that these oligosaccharides contribute to the reduced duration of rotavirus-induced diarrhea in pigs.Objective: We measured the effects of HMOs and prebiotic oligosaccharides on immune cell populations from noninfected and rotavirus-infected pigs. We hypothesized that dietary HMOs would modulate systemic and gastrointestinal immunity.Methods: Colostrum-deprived newborn pigs were fed formula, formula with 4 g HMOs/L (2'-fucosyllactose, lacto-N-neotetraose, 6'-sialyllactose, 3'-sialyllactose, and free sialic acid), or formula with 3...
June 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28482391/-two-families-of-x-linked-lymphoproliferative-disease-type-1-characterized-by-agammaglobulinemia
#12
W Y Li, J S Chen, Q Zhao, R X Dai, Y P Wang, H Y Zhao, X M Chen, X H Xue, X Y Sun, X M Tang, Y Zhang, Y Ding, X D Zhao, Z Y Zhang
Objective: To investigate the clinical and immunological laboratory features, mutations in SH2D1A gene and SAP protein expression in four children of two families with X-linked lymphoproliferative disease type 1(XLP-1). Method: Four patients (Family A including Patient 1 and Patient 2, Family B including Patient 3 and Patient 4) and their maternal relatives were enrolled in this study. The clinical manifestation, EBV infection status and chest CT scan were analyzed. The absolute and relative numbers of lymphocyte subsets, T lymphocyte proliferative response, SAP protein expression were assessed by flow cytometry...
May 4, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/28477078/memory-b-cells-and-response-to-abatacept-in-rheumatoid-arthritis
#13
Pierre Gazeau, Guillermo Carvajal Alegria, Valérie Devauchelle-Pensec, Christophe Jamin, Julie Lemerle, Boutahar Bendaoud, Wesley H Brooks, Alain Saraux, Divi Cornec, Yves Renaudineau
Abatacept is a fusion protein (CTLA4-Ig) and therapeutic molecule labeled for the treatment of rheumatoid arthritis (RA). Abatacept acts both by disrupting the CD28-mediated activation of T cells and by interacting with CD80/CD86 molecules present on antigen presenting cells such as monocytes and memory B cells. Accordingly and to evaluate clinical and biological parameters associated with response to abatacept, a retrospective monocentric study was conducted in 43 patients with RA, and the clinical response was evaluated at 6 months according to EULAR response criteria...
May 5, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28475279/nk-cells-generate-memory-type-responses-to-human-cytomegalovirus-infected-fibroblasts
#14
Nicholas Newhook, Neva Fudge, Michael Grant
Natural killer (NK) cells are cytotoxic lymphocytes that selectively respond against abnormal cells. Human cytomegalovirus (HCMV) infection causes expansion of NKG2C(+) CD57(+) NK cells in vivo and NKG2C(+) NK cells proliferate when cultured with HCMV-infected cells. This raises the possibility of an NK-cell subset selectively responding against a specific pathogen and accruing memory. To test this possibility, we compared proliferation, natural cytotoxicity and interferon-γ (IFN-γ) production of NK cells from HCMV-seropositive and HCMV-seronegative individuals co-cultured with HCMV-infected or uninfected MRC-5 cells...
May 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28474288/could-lymphocyte-profiling-be-useful-to-diagnose-systemic-autoimmune-diseases
#15
REVIEW
Guillermo Carvajal Alegria, Pierre Gazeau, Sophie Hillion, Claire I Daïen, Divi Y K Cornec
Considering the implications of B, T, and natural killer (NK) cells in the pathophysiology of systemic autoimmune diseases, the assessment of their distribution in the blood could be helpful for physicians in the complex process of determining a precise diagnosis. In primary Sjögren's syndrome, transitional and active naive B cells are increased and memory B cells are decreased compared to healthy controls and other systemic diseases. However, their utility to improve the accuracy of classification criteria has not been proven...
May 4, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28435674/the-three-rs-recruitment-retention-and-residence-of-leukocytes-in-the-liver
#16
REVIEW
Hayley A McNamara, Ian A Cockburn
The composition of leukocytes in the liver is highly distinct from that of the blood and lymphoid organs. In particular, the liver is highly enriched in non-conventional T cells such as natural killer T (NKT) cells, γδ T cells and mucosal-associated invariant T cells. In addition, there are significant populations of tissue-resident NK cells (or innate lymphoid cells (ILC1)) and memory CD8(+) T cells. These cells are joined in conditions of inflammation by neutrophils, monocytes and macrophages. In recent years a multitude of studies have generated insights into how these cells arrest, move and remain resident in the liver...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28431111/correction-of-abnormal-b-cell-subset-distribution-by-interleukin-6-receptor-blockade-in-polymyalgia-rheumatica
#17
Guillermo Carvajal Alegria, Valérie Devauchelle-Pensec, Yves Renaudineau, Alain Saraux, Jacques-Olivier Pers, Divi Cornec
Objectives.: The aim was to study lymphocyte subsets and circulating cytokines at diagnosis of PMR and after tocilizumab monotherapy. Methods.: Eighteen untreated patients with PMR were included in a prospective study and received 3-monthly tocilizumab infusions without glucocorticoids. Lymphocyte subset distribution was assessed by flow cytometry and serum cytokines were assayed by a 34-cytokine array and ELISA, at baseline and during follow-up. Baseline data were also compared with age- and sex-matched controls...
April 20, 2017: Rheumatology
https://www.readbyqxmd.com/read/28427548/autosomal-dominant-gain-of-function-stat1-mutation-and-severe-bronchiectasis
#18
Oded Breuer, Hagit Daum, Malena Cohen-Cymberknoh, Susanne Unger, David Shoseyov, Polina Stepensky, Baerbel Keller, Klaus Warnatz, Eitan Kerem
BACKGROUND: In a substantial number of patients with non-cystic fibrosis (CF) bronchiectasis an etiology cannot be found. Various complex immunodeficiency syndromes account for a significant portion of these patients but the mechanism elucidating the predisposition for suppurative lung disease often remains unknown. OBJECTIVE: To investigate the cause and mechanism predisposing a patient to severe bronchiectasis. METHODS: A patient presenting with severe non-CF bronchiectasis was investigated...
May 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28426690/phenotypic-characterization-and-anticancer-capacity-of-cd8-cytokine-induced-killer-cells-after-antigen-induced-expansion
#19
Jianhua Liu, Lu Wang, Yaoling Wang, Wenjie Zhang, Yilin Cao
Cytokine-induced killer cells (CIK) have been used in clinic for adoptive immunotherapy in a variety of malignant tumors and have improved the prognosis of cancer patients. However, there are individual differences in the CIK cell preparations including the obvious differences in the ratio of effector CIK cells among different cancer patients. Infusion of such heterogeneous immune cell preparation is an important factor that would affect the therapeutic efficacy. We report here the enrichment and expansion of CD8+ cells from CIK cells cultured for one week using magnetic activated cell sorting (MACS)...
2017: PloS One
https://www.readbyqxmd.com/read/28422756/%C3%AE-catenin-and-pi3k%C3%AE-inhibition-expands-precursor-th17-cells-with-heightened-stemness-and-antitumor-activity
#20
Kinga Majchrzak, Michelle H Nelson, Jacob S Bowers, Stefanie R Bailey, Megan M Wyatt, John M Wrangle, Mark P Rubinstein, Juan C Varela, Zihai Li, Richard A Himes, Sherine S L Chan, Chrystal M Paulos
ICOS costimulation generates Th17 cells with durable memory responses to tumor. Herein, we found that ICOS induces PI3K/p110δ/Akt and Wnt/β-catenin pathways in Th17 cells. Coinhibiting PI3Kδ and β-catenin altered the biological fate of Th17 cells. Th17 cells inhibited of both pathways expressed less RORγt, which, in turn, reduced their ability to secrete IL-17. Unexpectedly, these cells were more effective (than uninhibited cells) at regressing tumor when infused into mice, leading to long-term curative responses...
April 20, 2017: JCI Insight
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