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Naïve T cells

Gwennaelle Bodart, Khalil Farhat, Chantal Renard-Charlet, Guillaume Becker, Alain Plenevaux, Roberto Salvatori, Vincent Geenen, Henri Martens
A debate is still open about the precise control exerted by the somatotrope GH-releasing hormone (GHRH)/growth hormone (GH)/insulin-like growth factor 1 axis on the immune system. The objective of this study was to directly address this question through the use of Ghrh -/- mice that exhibit a severe deficiency of their somatotrope axis. After control backcross studies and normalization for the reduced global weight of transgenic mice, no difference in weight and cellularity of the thymus was observed in Ghrh -/- mice when compared with C57BL/6 wild-type (WT) control mice...
2018: Frontiers in Endocrinology
Josiane C S Mapplebeck, Rebecca Dalgarno, YuShan Tu, Orla Moriarty, Simon Beggs, Charlie H T Kwok, Katherine Halievski, Sofia Assi, Jeffrey S Mogil, Tuan Trang, Michael W Salter
Microglia-neuron signalling in the spinal cord is a key mediator of mechanical allodynia caused by peripheral nerve injury. We recently reported sex differences in microglia in pain signalling in mice: spinal mechanisms underlying nerve injury-induced allodynia are microglial dependent in male but not female mice. Whether this sex difference in pain hypersensitivity mechanisms is conserved in other species is unknown. Here, we show that in rats, the spinal mechanisms of nerve injury-induced hypersensitivity in males differ from those in females, with microglial P2X4 receptors (P2X4Rs) being a key point of divergence...
April 30, 2018: Pain
Daisuke Aki, Hui Li, Wen Zhang, Mingke Zheng, Chris Elly, Jee H Lee, Weiguo Zou, Yun-Cai Liu
The mechanisms by which the sensitivity of naive CD4+ T cells to stimulation by the cognate antigen via the T cell antigen receptor (TCR) determines their differentiation into distinct helper T cell subsets remain elusive. Here we demonstrate functional collaboration of the ubiquitin E3 ligases Itch and WWP2 in regulating the strength of the TCR signal. Mice lacking both Itch and WWP2 in T cells showed spontaneous autoimmunity and lung inflammation. CD4+ T cells deficient in Itch and WWP2 exhibited hypo-responsiveness to TCR stimulation and a bias toward differentiation into the TH 2 subset of helper T cells...
June 20, 2018: Nature Immunology
Viktor Schneidt, Marta Ilecka, Peter Dreger, Dwain G van Zyl, Susanne Fink, Josef Mautner, Henri-Jacques Delecluse
Chronic lymphocytic leukemia (CLL) is the most frequent B cell malignancy in Caucasian adults. The therapeutic armamentarium against this incurable disease has recently seen a tremendous expansion with the introduction of specific pathway inhibitors and innovative immunotherapy. However, none of these approaches is curative and devoid of side effects. We have used B-cell-specific antibodies conjugated with antigens (AgAbs) of the Epstein-Barr virus (EBV) to efficiently expand memory CD4+ cytotoxic T lymphocytes (CTLs) that recognized viral epitopes in 12 treatment-naive patients with CLL...
June 20, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Egidio Brocca-Cofano, Cuiling Xu, Katherine S Wetzel, Mackenzie L Cottrell, Benjamin B Policicchio, Kevin D Raehtz, Dongzhu Ma, Tammy Dunsmore, George S Haret-Richter, Karam Musaitif, Brandon F Keele, Angela D Kashuba, Ronald G Collman, Ivona Pandrea, Cristian Apetrei
Current approaches do not eliminate all HIV-1 maternal-to-infant transmissions (MTIT); new prevention paradigms might help avert new infections. We administered Maraviroc (MVC) to rhesus macaques (RMs) to block CCR5-mediated entry, followed by repeated oral exposure of a CCR5-dependent clone of simian immunodeficiency virus (SIV)mac251 (SIVmac766). MVC significantly blocked the CCR5 coreceptor in peripheral blood mononuclear cells and tissue cells. All control animals and 60% of MVC-treated infant RMs became infected by the 6th challenge, with no significant difference between the number of exposures (p=0...
June 20, 2018: Journal of Virology
Kylie M Quinn, Annette Fox, Kim L Harland, Brendan E Russ, Jasmine Li, Thi H O Nguyen, Liyen Loh, Moshe Olshanksy, Haroon Naeem, Kirill Tsyganov, Florian Wiede, Rosela Webster, Chantelle Blyth, Xavier Y X Sng, Tony Tiganis, David Powell, Peter C Doherty, Stephen J Turner, Katherine Kedzierska, Nicole L La Gruta
Age-associated decreases in primary CD8+ T cell responses occur, in part, due to direct effects on naive CD8+ T cells to reduce intrinsic functionality, but the precise nature of this defect remains undefined. Aging also causes accumulation of antigen-naive but semi-differentiated "virtual memory" (TVM ) cells, but their contribution to age-related functional decline is unclear. Here, we show that TVM cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naive T cells (TN cells) retain proliferative capacity in both aged mice and humans...
June 19, 2018: Cell Reports
Hung Cao Dinh, Ivan Bautmans, Ingo Beyer, Tony Mets, Oscar Okwudiri Onyema, Louis Nuvagah Forti, Wim Renmans, Sam Vander Meeren, Kristin Jochmans, Sofie Vermeiren, Roberta Vella Azzopardi, Rose Njemini
Frailty is highly prevalent in old age and confers an important mortality risk. Although the causes of frailty are multiple, immuno-senescence (IS) - predominantly driven by cytomegalovirus (CMV) - has been implicated in its pathophysiology. Thus far, research examining the association between IS and frailty states is sparse and equivocal. On the other hand, evidence is mounting in support of the view that frailty can be reversed, especially for those in the pre-frail stage. Therefore, we aimed to clarify the impact of CMV on IS and its relevance to pre-frailty...
June 19, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Kentaro Serizawa, Hirokazu Tanaka, Yasuyoshi Morita, Takahide Taniguchi, Takashi Ashida, Itaru Matsumura
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic stem cells, characterized by dysplastic hematopoiesis and dysregulated immune system resulting in various clinical conditions. Paraneoplastic inflammatory syndromes, which are well known to be associated with MDS, show response to immune-modulated therapy and often disappear during the course of hematologic management. Azacitidine (5-Aza) was shown to prolong survival of high-risk MDS patients, however, the effects of 5-Aza on paraneoplastic inflammation in MDS have yet to be elucidated...
2018: Frontiers in Oncology
Anna Sanecka, Nagisa Yoshida, Elizabeth Motunrayo Kolawole, Harshil Patel, Brian D Evavold, Eva-Maria Frickel
T cell receptor-major histocompatibility complex (TCR-MHC) affinities span a wide range in a polyclonal T cell response, yet it is undefined how affinity shapes long-term properties of CD8 T cells during chronic infection with persistent antigen. Here, we investigate how the affinity of the TCR-MHC interaction shapes the phenotype of memory CD8 T cells in the chronically Toxoplasma gondii- infected brain. We employed CD8 T cells from three lines of transnuclear (TN) mice that harbor in their endogenous loci different T cell receptors specific for the same Toxoplasma antigenic epitope ROP7...
2018: Frontiers in Immunology
Yuxia Zhang, Jovana Maksimovic, Bing Huang, David Peter De Souza, Gaetano Naselli, Huan Chen, Li Zhang, Kai Weng, Hanquan Liang, Yanhui Xu, John M Wentworth, Nicholas D Huntington, Alicia Oshlack, Sitang Gong, Axel Kallies, Peter Vuillermin, Min Yang, Leonard C Harrison
How T cells differentiate in the neonate may critically determine the ability of the infant to cope with infections, respond to vaccines and avert allergies. Previously, we found that naïve cord blood CD4+ T cells differentiated toward an IL-4-expressing phenotype when activated in the presence of TGF-β and monocyte-derived inflammatory cytokines, the latter are more highly secreted by infants who developed food allergy. Here, we show that in the absence of IL-2 or IL-12, naïve cord blood CD8+ T cells have a natural propensity to differentiate into IL-4-producing non-classic TC 2 cells when they are activated alone, or in the presence of TGF-β and/or inflammatory cytokines...
2018: Frontiers in Immunology
T Furuta, S Baba, M Yamade, T Uotani, T Kagami, T Suzuki, S Tani, Y Hamaya, M Iwaizumi, S Osawa, K Sugimoto
BACKGROUND: Although autoimmune gastritis (AIG) is generally considered relatively rare, we frequently encounter AIG among patients at to our hospital who have experienced at least two episodes of Helicobacter pylori eradication failure. AIMS: We investigated the incidence of AIG in consecutive patients who consulted our department for H. pylori eradication with reference to eradication history. METHODS: A total of 404 consecutive patients who visited the H...
June 19, 2018: Alimentary Pharmacology & Therapeutics
Tetsuya Itabashi, Yasunobu Arima, Daisuke Kamimura, Kotaro Higuchi, Yoshio Bando, Hiromi Takahashi-Iwanaga, Masaaki Murakami, Masahiko Watanabe, Toshihiko Iwanaga, Junko Nio-Kobayashi
Multiple sclerosis (MS) is an autoimmune disease in which pathogenic T cells play an important role, and an experimental autoimmune encephalomyelitis (EAE) is used as an animal model of MS. Galectins are β-galactoside-binding lectins and involved in various physiological and pathological events. Among fifteen members of galectins, galectin-1, -8, and -9 play immunosuppressive roles in MS and EAE; however, the role of galectin-3 (gal-3) is complex and controversial. We examined expression of gal-3 in the spinal cord and nerve roots of EAE mice...
June 16, 2018: Neurochemistry International
Sixtine Coindre, Nicolas Tchitchek, Lamine Alaoui, Bruno Vaslin, Christine Bourgeois, Cecile Goujard, Veronique Avettand-Fenoel, Camille Lecuroux, Pierre Bruhns, Roger Le Grand, Anne-Sophie Beignon, Olivier Lambotte, Benoit Favier
CD32a has been proposed as a specific marker of latently HIV-infected CD4+ T cells. However, CD32a was recently found to be expressed on CD4+ T cells of healthy donors, leading to controversy on the relevance of this marker in HIV persistence. Here, we used mass cytometry to characterize the landscape and variation in the abundance of CD32a+ CD4+ T cells during HIV infection. To this end, we analyzed CD32a+ CD4+ T cells in primary HIV infection before and after effective combination antiretroviral therapy (cART) and in healthy donors...
2018: Frontiers in Immunology
Ce Tang, Shigeru Kakuta, Kenji Shimizu, Motohiko Kadoki, Tomonori Kamiya, Tomoyuki Shimazu, Sachiko Kubo, Shinobu Saijo, Harumichi Ishigame, Susumu Nakae, Yoichiro Iwakura
The cytokines IL-17A and IL-17F have 50% amino-acid identity and bind the same receptor; however, their functional differences have remained obscure. Here we found that Il17f-/- mice resisted chemically induced colitis, but Il17a-/- mice did not, and that Il17f-/- CD45RBhi CD4+ T cells induced milder colitis in lymphocyte-deficient Rag2-/- mice, accompanied by an increase in intestinal regulatory T cells (Treg cells). Clostridium cluster XIVa in colonic microbiota capable of inducing Treg cells was increased in both Il17f-/- mice and mice given transfer Il17f-/- T cells, due to decreased expression of a group of antimicrobial proteins...
June 18, 2018: Nature Immunology
J M Schaenman, M Rossetti, T Sidwell, V Groysberg, G Sunga, Y Korin, E Liang, X Zhou, B Abdallah, E Lum, S Bunnapradist, T Pham, G Danovitch, E F Reed
Older kidney transplant recipients experience increased rates of infection and death, and less rejection, compared with younger patients. However, little is known about immune dysfunction in older compared with younger kidney transplant recipients and whether it is associated with infection. We evaluated T cell phenotypes including maturation, immune senescence, and exhaustion in a novel investigation into differences in older compared with younger patients receiving identical immune suppression regimens. We evaluated PBMC from 60 kidney transplant recipients (23 older and 37 matched younger patients) by multiparameter immune phenotyping...
June 15, 2018: Human Immunology
Amanda Soares Alves, Mayari Eika Ishimura, Yeda Aparecida de Oliveira Duarte, Valquiria Bueno
Aim: The increased number of individuals older than 80 years, centenarians, and supercentenarians is not a synonym for healthy aging, since severe infections, hospitalization, and disability are frequently observed. In this context, a possible strategy is to preserve the main characteristics/functions of the immune system with the aim to cause less damage to the organism during the aging process. Vitamin D acts on bone marrow, brain, breast, malignant cells, and immune system and has been recommended as a supplement...
2018: Frontiers in Immunology
Kenjiro Adachi, Wolfgang Kopp, Guangming Wu, Sandra Heising, Boris Greber, Martin Stehling, Marcos J Araúzo-Bravo, Stefan T Boerno, Bernd Timmermann, Martin Vingron, Hans R Schöler
Transcription factor (TF)-mediated reprogramming to pluripotency is a slow and inefficient process, because most pluripotency TFs fail to access relevant target sites in a refractory chromatin environment. It is still unclear how TFs actually orchestrate the opening of repressive chromatin during the long latency period of reprogramming. Here, we show that the orphan nuclear receptor Esrrb plays a pioneering role in recruiting the core pluripotency factors Oct4, Sox2, and Nanog to inactive enhancers in closed chromatin during the reprogramming of epiblast stem cells...
June 11, 2018: Cell Stem Cell
Gemma D Banham, Shaun M Flint, Nicholas Torpey, Paul A Lyons, Don N Shanahan, Adele Gibson, Christopher J E Watson, Ann-Marie O'Sullivan, Joseph A Chadwick, Katie E Foster, Rachel B Jones, Luke R Devey, Anna Richards, Lars-Peter Erwig, Caroline O Savage, Kenneth G C Smith, Robert B Henderson, Menna R Clatworthy
BACKGROUND: B cells produce alloantibodies and activate alloreactive T cells, negatively affecting kidney transplant survival. By contrast, regulatory B cells are associated with transplant tolerance. Immunotherapies are needed that inhibit B-cell effector function, including antibody secretion, while sparing regulators and minimising infection risk. B lymphocyte stimulator (BLyS) is a cytokine that promotes B-cell activation and has not previously been targeted in kidney transplant recipients...
June 14, 2018: Lancet
Norah L Smith, Ravi K Patel, Arnold Reynaldi, Jennifer K Grenier, Jocelyn Wang, Neva B Watson, Kito Nzingha, Kristel J Yee Mon, Seth A Peng, Andrew Grimson, Miles P Davenport, Brian D Rudd
Heterogeneity is a hallmark feature of the adaptive immune system in vertebrates. Following infection, naive T cells differentiate into various subsets of effector and memory T cells, which help to eliminate pathogens and maintain long-term immunity. The current model suggests there is a single lineage of naive T cells that give rise to different populations of effector and memory T cells depending on the type and amounts of stimulation they encounter during infection. Here, we have discovered that multiple sub-populations of cells exist in the naive CD8+ T cell pool that are distinguished by their developmental origin, unique transcriptional profiles, distinct chromatin landscapes, and different kinetics and phenotypes after microbial challenge...
June 6, 2018: Cell
Magdalena Kowalewicz-Kulbat, Piotr Szpakowski, Camille Locht, Franck Biet, Paulina Kaplonek, Krzysztof T Krawczyk, Joël Pestel, Wieslawa Rudnicka
Bacillus Calmette-Guérin (BCG) is the only vaccine available against tuberculosis and the tuberculin skin test (TST) is the most widely used method to detect BCG take. However, subjects may remain TST-negative, even after several BCG administrations. To investigate some of the potential reasons underlying this inability of developing tuberculin sensitivity in response to BCG we compared the effect of different mycobacterial stimuli in the groups differently responding to tuberculin. TST was performed on 71 healthy adults aged 25-30 years, who had received BCG in their childhood, and considered TST-positive at ≥10 mm...
June 13, 2018: Vaccine
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