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CD8 memory

Sven Jarius, Marius Ringelstein, Jürgen Haas, Irina I Serysheva, Lars Komorowski, Kai Fechner, Klaus-Peter Wandinger, Philipp Albrecht, Harald Hefter, Andreas Moser, Eva Neuen-Jacob, Hans-Peter Hartung, Brigitte Wildemann, Orhan Aktas
BACKGROUND: Recently, we described a novel autoantibody, anti-Sj/ITPR1-IgG, that targets the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in patients with cerebellar ataxia. However, ITPR1 is expressed not only by Purkinje cells but also in the anterior horn of the spinal cord, in the substantia gelatinosa and in the motor, sensory (including the dorsal root ganglia) and autonomic peripheral nervous system, suggesting that the clinical spectrum associated with autoimmunity to ITPR1 may be broader than initially thought...
October 24, 2016: Journal of Neuroinflammation
Mohammad Islamuddin, Garima Chouhan, Muzamil Yaqub Want, Hani A Ozbak, Hassan A Hemeg, Farhat Afrin
BACKGROUND: The therapy of visceral leishmaniasis (VL) is limited by resistance, toxicity and decreased bioavailability of the existing drugs coupled with dramatic increase in HIV-co-infection, non-availability of vaccines and down regulation of cell-mediated immunity (CMI). Thus, we envisaged combating the problem with plant-derived antileishmanial drug that could concomitantly mitigate the immune suppression of the infected hosts. Several plant-derived compounds have been found to exert leishmanicidal activity via immunomodulation...
October 2016: PLoS Neglected Tropical Diseases
Pleun Hombrink, Christina Helbig, Ronald A Backer, Berber Piet, Anna E Oja, Regina Stark, Giso Brasser, Aldo Jongejan, René E Jonkers, Benjamin Nota, Onur Basak, Hans C Clevers, Perry D Moerland, Derk Amsen, René A W van Lier
Tissue-resident memory T cells (TRM cells) in the airways mediate protection against respiratory infection. We characterized TRM cells expressing integrin αE (CD103) that reside within the epithelial barrier of human lungs. These cells had specialized profiles of chemokine receptors and adhesion molecules, consistent with their unique localization. Lung TRM cells were poised for rapid responsiveness by constitutive expression of deployment-ready mRNA encoding effector molecules, but they also expressed many inhibitory regulators, suggestive of programmed restraint...
October 24, 2016: Nature Immunology
Jennie Johnstone, Robin Parsons, Fernando Botelho, Jamie Millar, Shelly McNeil, Tamas Fulop, Janet E McElhaney, Melissa K Andrew, Stephen D Walter, P J Devereaux, Mehrnoush Malek, Ryan R Brinkman, Jonathan Bramson, Mark Loeb
OBJECTIVES: To determine whether immune phenotypes associated with immunosenescence are predictive of frailty and mortality within 1-year in elderly nursing home residents. DESIGN: Cross sectional study of frailty; prospective cohort study of mortality. SETTING: Thirty-two nursing homes in four Canadian cities between September 2009 and October 2011. PARTICIPANTS: Nursing home residents aged 65 and older (N = 1,072, median age 86, 72% female)...
October 24, 2016: Journal of the American Geriatrics Society
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
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