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Memory CD8

Emilia Pachulec, Vanessa Neitzke-Montinelli, João P B Viola
Nuclear factor of activated T cells (NFAT) 2 null mutant mice die in utero of cardiac failure, precluding analysis of the role of NFAT2 in lymphocyte responses. Only the NFAT2(-/-)/Rag-1(-/-) chimeric mice model gave insight into the role of NFAT2 transcription factor in T lymphocyte development, activation, and differentiation. As reports are mainly focused on the role of NFAT2 in CD4(+) T lymphocytes activation and differentiation, we decided to investigate NFAT2's impact on CD8(+) T lymphocyte responses...
2016: Frontiers in Immunology
Luciana Nahar Dos Santos, Pedro Henrique Lopes da Silva, Iris Maria Peixoto Alvim, José Augusto da Costa Nery, Flávio Alves Lara, Euzenir Nunes Sarno, Danuza Esquenazi
In spite of hyporesponsivity to Mycobacterium leprae, borderline lepromatous (BL) patients show clinical and immunological instability, and undergo frequent acute inflammatory episodes such as type 1 reaction (T1R), which may cause nerve damages. This work focused on the participation of T cell subsets from blood and skin at T1R onset. We observed a significantly increased ex vivo frequency of both effector and memory CD4+ and CD8+ T cells in T1R group. Besides, ex vivo frequency of T cell homing receptor, the Cutaneous Leukocyte-associated Antigen (CLA) was significantly increased in T cells from T1R patients...
2016: PloS One
Laura Rivino, Mei Qiu Lim
Dengue (DENV) and Zika viruses (ZIKV) are rapidly emerging mosquito-borne flaviviruses which represent a public health concern. Understanding host protective immunity to these viruses is critical for the design of optimal vaccines. Over a decade of research has highlighted a significant contribution of the T cell response to both protection and/or disease enhancement during dengue infection, the latter being mainly associated with sub-optimal cross-reactive T cell responses during secondary infections. Phase IIb/III clinical trials of the first licensed tetravalent dengue vaccine highlight increased vaccine efficacy in dengue-immune as opposed to dengue-naïve vaccinees, suggesting a possible immunoprotective role of pre-existing DENV-specific T cells that are boosted upon vaccination...
October 20, 2016: Immunology
Andrew J Highton, Adam Girardin, Georgia M Bell, Sarah M Hook, Roslyn A Kemp
BACKGROUND: Vaccination generating a robust memory population of CD8(+) T cells may provide protection against cancer. However, immune therapies for cancer are influenced by the local tumour immune microenvironment. An infiltrate of T cells into tumours of people with colorectal cancer has proven to be a significant indicator of good prognosis. METHODS: We used an intracaecal mouse model of cancer to determine whether a protective immune response against a mucosal gut tumour could be generated using a systemic intervention...
October 18, 2016: BMC Immunology
Maria Malm, Kirsi Tamminen, Timo Vesikari, Vesna Blazevic
Norovirus (NoV) is a leading cause of acute gastroenteritis in people of all ages worldwide. NoV-specific serum antibodies which block the binding of NoV virus-like particles (VLPs) to the cell receptors have been thoroughly investigated. In contrast, only a few publications are available on the NoV capsid VP1 protein-specific T cell responses in humans naturally infected with the virus. Freshly isolated peripheral blood mononuclear cells of eight healthy adult human donors previously exposed to NoV were stimulated with purified VLPs derived from NoV GII...
2016: Frontiers in Microbiology
Xu Shi, Ying Tang, Xiguang Sun, Yufei Liu, Ying Sun, Munan Sun, Yanfang Jiang, Yulin Li
The current study aimed to investigate the distribution of memory and naïve T cell (TN) subsets in hepatitis B virus (HBV)‑infected patients at different immune stages and investigate the effect of interleukin 33 (IL‑33) on the regulation of the T‑cell subsets. The distributions of memory and naïve T cells were detected by flow cytometry. ELISA was conducted to assess the levels of IL‑4, IL‑5, IL‑10, IL‑12, interferon γ and tumor necrosis factor α. The expression levels of IL‑33 and HBV x protein (HBx) were measured by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively...
October 13, 2016: Molecular Medicine Reports
Emma C Reilly, Kris Lambert-Emo, David J Topham
After disease resolution, a small subset of influenza specific CD8+ T cells can remain in the airways of the lung as a tissue resident memory population (TRM). These cells are critical for protection from subsequent infections with heterosubtypic influenza viruses. Although it is well established that expression of the collagen IV binding integrin alpha 1 is necessary for the retention and maintenance of TRM cells, other requirements allowing them to localize to the airways and persist are less well understood...
2016: PloS One
Aida S Hansen, Bettina B Bundgaard, Bjarne K Møller, Per Höllsberg
CD46 is a glycoprotein with important functions in innate and adaptive immune responses. Functionally different isoforms are generated by alternative splicing at exons 7-9 (BC and C isoforms) and exon 13 (CYT-1 and CYT-2 isoforms) giving rise to BC1, BC2, C1 and C2. We developed a novel real-time PCR assay that allows quantitative comparisons between these isoforms. Their relative frequency in CD4(+) T cells from 100 donors revealed a distribution with high interpersonally variability. Importantly, the distribution between the isoforms was not random and although splicing favoured inclusion of exon 8 (BC isoforms), exclusion of exon 8 (C isoforms) was significantly linked to exclusion of exon 13 (CYT-2 isoforms)...
October 14, 2016: Scientific Reports
Yang Liu, Srilakshmi Pandeswara, Vinh Dao, Álvaro Padrón, Justin M Drerup, Shunhua Lao, Aijie Liu, Vincent Hurez, Tyler J Curiel
mTOR drives tumor growth but also supports T cell function, rendering the applications of mTOR inhibitors complex especially in T cell malignancies. Here we studied the effects of the mTOR inhibitor rapamycin in mouse EL4 T cell lymphoma. Typical pharmacologic rapamycin (1-8 mg/kg) significantly reduced tumor burden via direct suppression of tumor cell proliferation and improved survival in EL4 challenge independent of anti-tumor immunity. Denileukin diftitox (DD)-mediated depletion of regulatory T cells significantly slowed EL4 growth in vivo in a T cell-dependent fashion...
October 13, 2016: Cancer Research
Mirjam A Lips, Jan Bert van Klinken, Hanno Pijl, Ignace Janssen, Ko Willems van Dijk, Frits Koning, Vanessa van Harmelen
INTRODUCTION: Weight loss interventions such as Roux-en-Y gastric bypass (RYGB) and very low calorie diets (VLCD) lead to improvement of glucose metabolism in obese individuals with type-2 diabetes. Weight loss can also positively influence the unfavorable inflammatory profile associated with obesity. However, a direct comparison of the effect of VLCD and RYGB on systemic inflammation is lacking. METHODS: Systemic inflammation was investigated in age- and BMI-matched morbidly obese T2DM women by determining the number and activation- or memory status of peripheral blood leukocytes by flow cytometry, in addition to measuring circulating levels of cytokines and CRP...
November 2016: Metabolism: Clinical and Experimental
Lexus R Johnson, Orr-El Weizman, Moritz Rapp, Sing Sing Way, Joseph C Sun
Despite robust secondary T cell expansion primed by vaccination, the impact on primary immune responses to heterotypic antigens remains undefined. Here we show that secondary expansion of epitope-specific memory CD8(+) T cells primed by prior infection with recombinant pathogens limits the primary expansion of naive CD8(+) T cells with specificity to new heterologous antigens, dampening protective immunity against subsequent pathogen challenge. The degree of naive T cell repression directly paralleled the magnitude of the recall response...
October 11, 2016: Cell Reports
Susanne G Oberle, Layane Hanna-El-Daher, Vijaykumar Chennupati, Sarah Enouz, Stefanie Scherer, Martin Prlic, Dietmar Zehn
Many infections are caused by pathogens that are similar, but not identical, to previously encountered viruses, bacteria, or vaccines. In such re-infections, pathogens introduce known antigens, which are recognized by memory T cells and new antigens that activate naive T cells. How preexisting memory T cells impact the repertoire of T cells responding to new antigens is still largely unknown. We demonstrate that even a minimum epitope overlap between infections strongly increases the activation threshold and narrows the diversity of T cells recruited in response to new antigens...
October 11, 2016: Cell Reports
Nargis Khan, Susanta Pahari, Aurobind Vidyarthi, Mohammad Aqdas, Javed N Agrewala
Tuberculosis (TB) is the leading cause of morbidity and mortality among all infectious diseases. Failure of Bacillus Calmette Guerin as a vaccine and serious side-effects and toxicity due to long-term TB drug regime are the major hurdles associated with TB control. The problem is further compounded by the emergence of drug-resistance strains of Mycobacterium tuberculosis (Mtb). Consequently, it demands a serious attempt to explore safer and superior treatment approaches. Recently, an improved understanding of host-pathogen interaction has opened up new avenues for immunotherapy for treating TB...
2016: Frontiers in Immunology
Tatiana Jofra, Roberta Di Fonte, Tarun Edgar Hutchinson, Farhad Dastmalchi, Giuseppe Galvani, Manuela Battaglia, Shahram Salek-Ardakani, Georgia Fousteri
PTPN22 (protein tyrosine phosphatase non receptor 22) encodes a tyrosine phosphatase that functions as a key regulator of immune homeostasis. In particular, PTPN22 inhibits T-cell receptor signaling and selectively promotes type I interferon responses in myeloid cells. To date, there is little information on the CD8 T-cell-intrinsic role of PTPN22 in response to a viral pathogen. We unexpectedly found that PTPN22-deficient virus-specific CD8 T cells failed to accumulate in wild-type hosts after lymphocytic choriomeningitis virus infection...
October 11, 2016: Immunology and Cell Biology
Michiel C van Aalderen, Ester B M Remmerswaal, Kirstin M Heutinck, Anja Ten Brinke, Mariet C W Feltkamp, Neelke C van der Weerd, Karlijn A M I van der Pant, Frederike J Bemelman, René A W van Lier, Ineke J M Ten Berge
Polyomavirus BK (BKPyV) frequently reactivates in immunosuppressed renal transplant recipients (RTRs) and may lead to graft loss due to BKPyV-induced interstitial nephritis (BKVN). Little is known on the differentiation of CD8+ T cells targeting BKPyV in RTRs. Here we investigated whether BKPyV-specific CD8+ T cell differentiation differs in RTRs with varying degrees of BKPyV reactivation and/or BKVN. Using combinatorial encoding with tetramers carrying BKPyV major capsid protein (VP1) and large T antigen protein (LTAG) epitopes, we investigated CD8+ T cell responses to BKPyV in longitudinally obtained PBMC samples from 46 HLA-A02-positive RTRs and 20 healthy adults...
October 2016: PLoS Pathogens
Y Zhang, C Ma, M Wang, H Hou, L Cui, C Jiang, J Sun, X Qu
BACKGROUND: The role of the interaction between tumor cells and inflammatory cells in gallbladder carcinoma (GBC) is unclear. Inflammatory cells exist in both the tumor immune microenvironment and the host peripheral blood circulatory system. In the current study, we examined the prognostic value of inflammatory cells in the tumor microenvironment and peripheral blood in patients with GBC. METHODS: 98 patients with GBC were recruited in this retrospective study...
October 7, 2016: Clinical & Translational Oncology
Romain Daillère, Marie Vétizou, Nadine Waldschmitt, Takahiro Yamazaki, Christophe Isnard, Vichnou Poirier-Colame, Connie P M Duong, Caroline Flament, Patricia Lepage, Maria Paula Roberti, Bertrand Routy, Nicolas Jacquelot, Lionel Apetoh, Sonia Becharef, Sylvie Rusakiewicz, Philippe Langella, Harry Sokol, Guido Kroemer, David Enot, Antoine Roux, Alexander Eggermont, Eric Tartour, Ludger Johannes, Paul-Louis Woerther, Elisabeth Chachaty, Jean-Charles Soria, Encouse Golden, Silvia Formenti, Magdalena Plebanski, Mutsa Madondo, Philip Rosenstiel, Didier Raoult, Vincent Cattoir, Ivo Gomperts Boneca, Mathias Chamaillard, Laurence Zitvogel
The efficacy of the anti-cancer immunomodulatory agent cyclophosphamide (CTX) relies on intestinal bacteria. How and which relevant bacterial species are involved in tumor immunosurveillance, and their mechanism of action are unclear. Here, we identified two bacterial species, Enterococcus hirae and Barnesiella intestinihominis that are involved during CTX therapy. Whereas E. hirae translocated from the small intestine to secondary lymphoid organs and increased the intratumoral CD8/Treg ratio, B. intestinihominis accumulated in the colon and promoted the infiltration of IFN-γ-producing γδT cells in cancer lesions...
September 28, 2016: Immunity
Sabine Tischer, René Geyeregger, Julian Kwoczek, Albert Heim, Constanca Figueiredo, Rainer Blasczyk, Britta Maecker-Kolhoff, Britta Eiz-Vesper
BACKGROUND: Human adenovirus (HAdV) infections remain a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Efficient antiviral T-cell responses are necessary to clear infection, which is hampered by delayed immune reconstitution and medical immunosuppression after HSCT. Protective immunity may be conferred by adoptive transfer of HAdV-specific T cells. For identification of patients at risk and monitoring of treatment responses diligent assessment of anti-HAdV cellular immune responses is crucial...
October 7, 2016: Journal of Translational Medicine
Natascha Luther, Fatemeh Shahneh, Melanie Brähler, Franziska Krebs, Sven Jäckel, Saravanan Subramaniam, Christian Stanger, Tanja Schönfelder, Bettina Kleis-Fischer, Christoph Reinhardt, Hans C Probst, Philip Wenzel, Katrin Schäfer, Christian Becker
RATIONALE: Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and non-immune cell function, however their role in sterile inflammation in venous thrombosis has not been systematically examined. OBJECTIVE: This study investigated the recruitment, activation and inflammatory activity of T cells in deep vein thrombosis (DVT) and its consequences for venous thrombus resolution. METHODS AND RESULTS: CD4(+) and CD8(+) T cells infiltrate the thrombus and vein wall rapidly upon DVT induction and remain in the tissue throughout thrombus resolution...
October 5, 2016: Circulation Research
Cara C Schafer, Yong Wang, Kenneth P Hough, Anandi Sawant, Stefan C Grant, Victor J Thannickal, Jaroslaw Zmijewski, Selvarangan Ponnazhagan, Jessy S Deshane
Indoleamine 2,3-dioxygenase (IDO) has been implicated in immune evasion by tumors. Upregulation of this tryptophan (Trp)-catabolizing enzyme, in tumor cells and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME), leads to Trp depletion that impairs cytotoxic T cell responses and survival; however, exact mechanisms remain incompletely understood. We previously reported that a combination therapy of gemcitabine and a superoxide dismutase mimetic promotes anti-tumor immunity in a mouse model of lung cancer by inhibiting MDSCs, enhancing polyfunctional response of CD8+ memory T cells, and extending survival...
September 26, 2016: Oncotarget
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