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https://www.readbyqxmd.com/read/28733484/cutting-edge-cd3-itam-diversity-is-required-for-optimal-tcr-signaling-and-thymocyte-development
#1
Matthew L Bettini, Po-Chein Chou, Clifford S Guy, Thomas Lee, Kate M Vignali, Dario A A Vignali
For the αβ or γδTCR chains to integrate extracellular stimuli into the appropriate intracellular cellular response, they must use the 10 ITAMs found within the CD3 subunits (CD3γε, CD3δε, and ζζ) of the TCR signaling complex. However, it remains unclear whether each specific ITAM sequence of the individual subunit (γεδζ) is required for thymocyte development or whether any particular CD3 ITAM motif is sufficient. In this article, we show that mice utilizing a single ITAM sequence (γ, ε, δ, ζa, ζb, or ζc) at each of the 10 ITAM locations exhibit a substantial reduction in thymic cellularity and limited CD4(-)CD8(-) (double-negative) to CD4(+)CD8(+) (double-positive) maturation because of low TCR expression and signaling...
July 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28625883/tcr-cd3-cd4-cd8-effector-t-cells-in-psoriasis
#2
D Brandt, M Sergon, S Abraham, K Mäbert, C M Hedrich
The autoimmune/inflammatory disorder psoriasis is characterized by keratinocyte proliferation and immune cell infiltration of the skin. TCR(+)CD3(+)CD4(-)CD8(-) "double negative" (DN) T cells can derive from CD8(+) T cells through the down-regulation of CD8. The inhibitory molecule programmed death (PD-)1 is expressed on activated T cells and plays a role in the maintenance of peripheral tolerance. A subset of DN T cells, characterized by the expression of PD-1, has recently been demonstrated to be self-reactive...
June 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28614208/il-8-expression-in-granulocytic-epithelial-lesions-of-idiopathic-duct-centric-pancreatitis-type-2-autoimmune-pancreatitis
#3
Yuna Ku, Seung-Mo Hong, Kohei Fujikura, Sung Joo Kim, Masayuki Akita, Shiho Abe-Suzuki, Hideyuki Shiomi, Atsuhiro Masuda, Tomoo Itoh, Takeshi Azuma, Myung-Hwan Kim, Yoh Zen
Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (P<0...
August 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28468970/concomitant-disruption-of-cd4-and-cd8-genes-facilitates-the-development-of-double-negative-%C3%AE-%C3%AE-tcr-peripheral-t-cells-that-respond-robustly-to-staphylococcal-superantigen
#4
Vaidehi R Chowdhary, Ashton Krogman, Ashenafi Y Tilahun, Mariam P Alexander, Chella S David, Govindarajan Rajagopalan
Mature peripheral double negative T (DNT) cells expressing αβ TCR but lacking CD4/CD8 coreceptors play protective as well as pathogenic roles. To better understand their development and functioning in vivo, we concomitantly inactivated CD4 and CD8 genes in mice with intact MHC class I and class II molecules with the hypothesis that this would enable the development of DNT cells. We also envisaged that these DNT cells could be activated by bacterial superantigens in vivo as activation of T cells by superantigens does not require CD4 and CD8 coreceptors...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28468680/cd3-cd4-neg-cd8-neg-double-negative-t-lymphocytes-and-nkt-cells-as-the-main-cytotoxic-related-cd107a-cells-in-lesions-of-cutaneous-leishmaniasis-caused-by-leishmania-viannia-braziliensis
#5
Raquel Ferraz, Clarissa F Cunha, Maria Inês F Pimentel, Marcelo R Lyra, Tatiana Pereira-Da-Silva, Armando O Schubach, Alda Maria Da-Cruz, Alvaro Luiz Bertho
BACKGROUND: Cutaneous leishmaniasis (CL) is caused by Leishmania (Viannia) braziliensis, which infects dermal macrophages and dendritic cells, causing an intense immune-mediated-tissue inflammation and a skin ulcer with elevated borders that can heal spontaneously or after antimonial therapy. The resolution of lesions depends on an adaptive immune response, and cytotoxic cells seem to have a fundamental role in this process. The aim of this study is to better understand the role of cytotoxicity mediated mechanisms that occur during the immune response in the CL lesion milieu, considering distinct cytotoxic-related CD107a(+) cells, such as CD8(+), CD4(+), CD4(neg) CD8(neg) (double-negative, DN) and CD4(+)CD8(+) (double-positive, DP) T lymphocytes, as well as NK and NKT cells...
May 3, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28166225/the-composition-of-t-cell-subtypes-in-duodenal-biopsies-are-altered-in-coeliac-disease-patients
#6
Janni V Steenholt, Christian Nielsen, Leen Baudewijn, Anne Staal, Karina S Rasmussen, Hardee J Sabir, Torben Barington, Steffen Husby, Henrik Toft-Hansen
One of the hallmarks of Celiac disease (CD) is intraepithelial lymphocytosis in the small intestine. Until now, investigations to characterize the T cell subpopulations within the epithelial layer have not discriminated between the heterodimeric co-receptor molecule, CD8αβ, and the possibly immunoregulatory CD8αα homodimer molecule. Besides TCRαβ+ CD4+ cells, no other phenotypes have been shown to be gluten-reactive. Using flow cytometry on lymphocytes from duodenal biopsies, we determined that the number of B cells (CD3- CD19+) and the number of CD3+ CD4- CD8- double-negative (DN) T cells were elevated 6-7 fold in children with CD...
2017: PloS One
https://www.readbyqxmd.com/read/28159903/cd31-a-valuable-marker-to-identify-early-and-late-stages-of-t-cell-differentiation-in-the-human-thymus
#7
Marc Douaisi, Rachel S Resop, Maho Nagasawa, Joshua Craft, Beth D Jamieson, Bianca Blom, Christel H Uittenbogaart
Although CD31 expression on human thymocytes has been reported, a detailed analysis of CD31 expression at various stages of T cell development in the human thymus is missing. In this study, we provide a global picture of the evolution of CD31 expression from the CD34(+) hematopoietic precursor to the CD45RA(+) mature CD4(+) and CD8(+) single-positive (SP) T cells. Using nine-color flow cytometry, we show that CD31 is highly expressed on CD34(+) progenitors and stays high until the early double-positive stage (CD3(-)CD4(+)CD8α(+)β(-))...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28091621/differential-susceptibility-and-maturation-of-thymocyte-subsets-during-salmonella-typhimurium-infection-insights-on-the-roles-of-glucocorticoids-and-interferon-gamma
#8
Shamik Majumdar, Mukta Deobagkar-Lele, Vasista Adiga, Abinaya Raghavan, Nitin Wadhwa, Syed Moiz Ahmed, Supriya Rajendra Rananaware, Subhashish Chakraborty, Omana Joy, Dipankar Nandi
The thymus is known to atrophy during infections; however, a systematic study of changes in thymocyte subpopulations has not been performed. This aspect was investigated, using multi-color flow cytometry, during oral infection of mice with Salmonella Typhimurium (S. Typhimurium). The major highlights are: First, a block in the developmental pathway of CD4(-)CD8(-) double negative (DN) thymocytes is observed. Second, CD4(+)CD8(+) double positive (DP) thymocytes, mainly in the DP1 (CD5(lo)CD3(lo)) and DP2 (CD5(hi)CD3(int)), but not DP3 (CD5(int)CD3(hi)), subsets are reduced...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28018346/low-double-negative-cd3-cd4-cd8-t-cells-are-associated-with-incomplete-restoration-of-cd4-t-cells-and-higher-immune-activation-in-hiv-1-immunological-non-responders
#9
Xiaofan Lu, Bin Su, Huan Xia, Xin Zhang, Zhiying Liu, Yunxia Ji, Zixuan Yang, Lili Dai, Luzia M Mayr, Christiane Moog, Hao Wu, Xiaojie Huang, Tong Zhang
Failure of immune reconstitution increases the risk of AIDS or non-AIDS related morbidity and mortality in HIV-1-infected patients. CD3(+)CD4(-)CD8(-) T cells, which are usually described as double-negative (DN) T cells, display CD4-like helper and immunoregulatory functions. Here, we have measured the percentage of DN T cells in the immune reconstituted vs. non-immune reconstituted HIV-1-infected individuals. We observed that immunological non-responders (INRs) had a low number of DN T cells after long-term antiretroviral therapy (ART), and the number of these cells positively correlated with the CD4(+) T cell count...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27999236/cd8-t-lymphocyte-subsets-in-bladder-tumor-draining-lymph-nodes
#10
Zahra Faghih, Saeideh Sadat Shobeiri, Ali Ariafar, Mohsen Sarkarian, Shahryar Zeighami, Nazanin Nazari, Saeed Abbasi-Sarvak, Nasrollah Erfani
BACKGROUND: Cytotoxic CD8+ T cells, as essential parts of the adaptive immune system, play pivotal roles in anti-tumor immune responses. It is well documented that cytokine expression profiles and activation status of these cells during anti-tumor immune responses affect the outcome of host-tumor interaction. OBJECTIVE: To investigate the percentages of CD8+ lymphocytes and their subsets in tumor draining lymph nodes of patients with bladder cancer. METHODS: Forty-five patients with bladder cancer, candidate for radical cystectomy, were recruited...
December 2016: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/27979843/unexplained-lymphadenopathies-autoimmune-lymphoproliferative-syndrome-in-an-adult-patient
#11
Fatima Leal-Seabra, Gonçalo Sarmento Costa, Henrique Pereira Coelho, Agripino Oliveira
Autoimmune lymphoproliferative syndrome (ALPS) is characterised by massive enlargement of the lymphoid organs, autoimmune cytopenias and a predisposition to develop lymphoid malignancies. The basic defect is a disturbance of the lymphocyte apoptosis, and a high number of circulating TCRab CD3(+)CD4(-)CD8(-) T-cells (double-negative T cells (DNT cells)). We describe a case of a 41-year-old man with fever, hepatosplenomegaly, multiple lymphadenopathy, autoimmune haemolytic anaemia and severe thrombocytopenia...
December 15, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27890077/t-lymphocyte-immunophenotypes-in-the-cerebrospinal-fluid-of-dogs-with-visceral-leishmaniasis
#12
Fernanda G Grano, José Eduardo Dos S Silva, Guilherme D Melo, Juliana Perosso, Valéria M F Lima, Gisele F Machado
Visceral leishmaniasis (VL) is a disease causing several clinical manifestations in dogs, including neurological disorders. Nevertheless, there are few studies related to the evaluation of the brain alterations during VL. Evidences of the involvement of cerebral barriers in infected dogs was reported, including the presence of brain inflammatory infiltrate, with a predominance of CD3+ T cells. Therefore, the aim of this study was to determine the immunophenotypes of T lymphocytes in the cerebrospinal fluid (CSF), as well as in peripheral blood, and to correlate with brain alterations in dogs with VL...
December 15, 2016: Veterinary Parasitology
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
#13
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/27856426/cytotoxic-t-cells-in-pd-l1-positive-malignant-pleural-mesotheliomas-are-counterbalanced-by-distinct-immunosuppressive-factors
#14
Mark M Awad, Robert E Jones, Hongye Liu, Patrick H Lizotte, Elena V Ivanova, Meghana Kulkarni, Grit S Herter-Sprie, Xiaoyun Liao, Abigail A Santos, Mark A Bittinger, Lauren Keogh, Shohei Koyama, Christina Almonte, Jessie M English, Julianne Barlow, William G Richards, David A Barbie, Adam J Bass, Scott J Rodig, F Stephen Hodi, Kai W Wucherpfennig, Pasi A Jänne, Lynette M Sholl, Peter S Hammerman, Kwok-Kin Wong, Raphael Bueno
PD-L1 immunohistochemical staining does not always predict whether a cancer will respond to treatment with PD-1 inhibitors. We sought to characterize immune cell infiltrates and the expression of T-cell inhibitor markers in PD-L1-positive and PD-L1-negative malignant pleural mesothelioma samples. We developed a method for immune cell phenotyping using flow cytometry on solid tumors that have been dissociated into single-cell suspensions and applied this technique to analyze 43 resected malignant pleural mesothelioma specimens...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27848183/an-atypical-case-of-late-onset-systemic-lupus-erythematosus-with-systemic-lymphadenopathy-and-severe-autoimmune-thrombocytopenia-neutropenia-mimicking-malignant-lymphoma
#15
Keita Tamaki, Satoko Morishima, Sawako Nakachi, Sakiko Kitamura, Sachie Uchibori, Shouhei Tomori, Taeko Hanashiro, Natsuki Shimabukuro, Iori Tedokon, Kazuho Morichika, Yukiko Nishi, Takeaki Tomoyose, Kennosuke Karube, Takuya Fukushima, Hiroaki Masuzaki
Here, we report a rare case of systemic lupus erythematosus (SLE) with conspicuous manifestation of hematological abnormalities. At onset, the 52-year-old male patient showed systemic lymphadenopathy and splenomegaly, severe autoimmune thrombocytopenia, and autoimmune neutropenia. Bone marrow examination and lymph node biopsy excluded the possibility of malignant lymphoma. Based on laboratory findings, he was finally diagnosed with combined autoimmune cytopenia coupled with SLE. Atypical clinical manifestations of SLE prompted us to explore the possibility of autoimmune lymphoproliferative syndrome (ALPS)...
April 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/27814766/antibody-dependent-cd56-t-cell-responses-are-functionally-impaired-in-long-term-hiv-1-infection
#16
Xueying Fan, Liyan Zhu, Hua Liang, Zhe Xie, Xiangbo Huang, Shuo Wang, Tao Shen
BACKGROUND: Antibody-dependent cellular cytotoxicity (ADCC), which mainly mediated by natural killer (NK) cells, may play a critical role in slowing human immunodeficiency virus type-1 (HIV-1) disease progression and protecting from HIV-1 infection. Besides classic NK cells, CD56+ T cells also have some NK cell-like properties, such as the large granular lymphocyte morphology and the capacity to destroy NK-sensitive target cells. However, little is known about the potentials of antibody-dependent CD56+ T cell responses and the association between antibody-dependent CD56+ T cell responses and HIV-1 disease progression...
November 4, 2016: Retrovirology
https://www.readbyqxmd.com/read/27769564/in-vivo-anti-inflammatory-activities-of-novel-cytokine-il-38-in-murphy-roths-large-mrl-lpr-mice
#17
Man Chu, Lai Shan Tam, Jing Zhu, Delong Jiao, De Hua Liu, Zhe Cai, Jie Dong, Christopher Wei Kai Lam, Chun Kwok Wong
The newly named interleukin (IL)-36 subfamily member IL-38 has been shown to exert anti-inflammatory activity. However, the in vivo immunomodulatory activity of IL-38 was poorly investigated in systemic lupus erythematosus (SLE). We have investigated the expression of CD4(+)IL-17(+) Th17, CD4(+)IFN-γ(+) Th1 and CD3(+)CD4(-)CD8(-) double negative (DN) T cells and the related immunopathological mechanisms in female MRL/lpr mice model of spontaneous lupus-like disease, with or without IL-38 treatment. Intravenous administration of murine recombinant IL-38 into MRL/lpr mice can ameliorate the lupus-like clinical symptoms including proteinuria, leukocyteuria and skin lesions...
March 2017: Immunobiology
https://www.readbyqxmd.com/read/27508670/-op-3d-04-activated-cd4-and-cd8-t-cell-subpopulations-in-patients-with-primary-hyperaldosteronism-and-true-resistant-hypertension
#18
A Kaszuba, A Konior, T Mikolajczyk, A Prejbisz, M Kabat, I Cendrowska-Demkow, P Dobrowolski, B Pregowska-Chwala, K Michel-Rowicka, A Klisiewicz, P Michalek, S Toutounchi, Z Galazka, M Reincke, A Januszewicz, Tj Guzik
OBJECTIVE: Role of the T cells in pathogenesis of hypertension has been demonstrated in numerous mouse models, limited data is available in human hypertension. Therefore the aim of our study was to quantify blood T lymphocyte subsets, characterized by expression of CD25 markers (CD3 + , CD8 + and CD3 + CD4-CD8- cells) and expression of perforin and granzyme (in CD8 + cells) in subjects with primary hyperaldosteronism (PA), resistant hypertension (RHT) characterized by increased cardiovascular risk and excessive amounts of circulating aldosterone in comparison to controls matched for age, sex and BMI(control group, CG)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27490802/cxcl9-and-cxcl10-predict-survival-and-are-regulated-by-cyclooxygenase-inhibition-in-advanced-serous-ovarian-cancer
#19
Holger Bronger, Judith Singer, Claudia Windmüller, Ute Reuning, Daniela Zech, Claire Delbridge, Julia Dorn, Marion Kiechle, Barbara Schmalfeldt, Manfred Schmitt, Stefanie Avril
BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are associated with improved survival in several epithelial cancers. The two chemokines CXCL9 and CXCL10 facilitate chemotactic recruitment of TILs, and their intratumoral accumulation is a conceivable way to improve TIL-dependent immune intervention in cancer. However, the prognostic impact of CXCL9 and CXCL10 in high-grade serous ovarian cancer (HGSC) is largely unknown. METHODS: One hundred and eighty four cases of HGSC were immunohistochemically analyzed for CXCL9, CXCL10...
August 23, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27457239/multiple-lesions-of-gastrointestinal-tract-invasion-by-monomorphic-epitheliotropic-intestinal-t-cell-lymphoma-accompanied-by-duodenal-and-intestinal-enteropathy-like-lesions-and-microscopic-lymphocytic-proctocolitis-a-case-series
#20
Hideki Ishibashi, Satoshi Nimura, Yoshiyuki Kayashima, Yasushi Takamatsu, Kunihiko Aoyagi, Naohiko Harada, Masanori Kadowaki, Takihiko Kamio, Shotaro Sakisaka, Morishige Takeshita
BACKGROUND: In East Asia, monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), previously known as type II enteropathy-associated T-cell lymphoma (EATL), occurs more frequently than type I EATL, and coeliac disease is rare. CASE PRESENTATION: Here we present four cases of MEITL in Japanese patients, including the endoscopic and pathological findings of their duodenal and colorectal lesions. Tumor specimens obtained from duodenal, intestinal, and colorectal biopsies in all four patients showed a diffuse intramucosal infiltration of small to/or medium-sized lymphoma cells and numerous atypical intraepithelial lymphocytes (IELs)...
July 25, 2016: Diagnostic Pathology
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