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https://www.readbyqxmd.com/read/28715973/the-molecular-basis-for-human-immunodeficiency-virus-latency
#1
Uri Mbonye, Jonathan Karn
Although potent combination antiretroviral therapy can effectively block viral replication in the host, human immunodeficiency virus (HIV) persists due to the existence of latent but replication-competent proviruses residing primarily in a very small population of resting memory CD4(+) T cells. Viral latency is established when the expression of the autoregulatory viral trans-activating factor Tat is reduced to subthreshold levels. The absence of Tat reduces HIV transcription and protein production to levels that make the host cell invisible to the immune system and refractory to antiretroviral treatment...
July 17, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28714465/enhanced-anti-tumour-immunity-requires-the-interplay-between-resident-and-circulating-memory-cd8-t-cells
#2
Michel Enamorado, Salvador Iborra, Elena Priego, Francisco J Cueto, Juan A Quintana, Sarai Martínez-Cano, Ernesto Mejías-Pérez, Mariano Esteban, Ignacio Melero, Andrés Hidalgo, David Sancho
The goal of successful anti-tumoural immunity is the development of long-term protective immunity to prevent relapse. Infiltration of tumours with CD8(+) T cells with a resident memory (Trm) phenotype correlates with improved survival. However, the interplay of circulating CD8(+) T cells and Trm cells remains poorly explored in tumour immunity. Using different vaccination strategies that fine-tune the generation of Trm cells or circulating memory T cells, here we show that, while both subsets are sufficient for anti-tumour immunity, the presence of Trm cells improves anti-tumour efficacy...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28710253/dual-immunization-with-sseb-flagellin-provides-enhanced-protection-against-salmonella-infection-mediated-by-circulating-memory-cells
#3
Seung-Joo Lee, Joseph Benoun, Brian S Sheridan, Zachary Fogassy, Oanh Pham, Quynh-Mai Pham, Lynn Puddington, Stephen J McSorley
The development of a subunit Salmonella vaccine has been hindered by the absence of detailed information about antigenic targets of protective Salmonella-specific T and B cells. Recent studies have identified SseB as a modestly protective Ag in susceptible C57BL/6 mice, but the mechanism of protective immunity remains undefined. In this article, we report that simply combining Salmonella SseB with flagellin substantially enhances protective immunity, allowing immunized C57BL/6 mice to survive for up to 30 d following challenge with virulent bacteria...
July 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28707003/up-regulation-of-lfa-1-allows-liver-resident-memory-t-cells-to-patrol-and-remain-in-the-hepatic-sinusoids
#4
H A McNamara, Y Cai, M V Wagle, Y Sontani, C M Roots, L A Miosge, J H O'Connor, H J Sutton, V V Ganusov, W R Heath, P Bertolino, C G Goodnow, I A Parish, A Enders, I A Cockburn
Liver-resident CD8+ T cells are highly motile cells that patrol the vasculature and provide protection against liver pathogens. A key question is: how can these liver CD8+ T cells be simultaneously present in the circulation and tissue-resident? Because liver-resident T cells do not express CD103 - a key integrin for T cell residence in epithelial tissues - we investigated other candidate adhesion molecules. Using intra-vital imaging we found that CD8+ T cell patrolling in the hepatic sinusoids is dependent upon LFA-1-ICAM-1 interactions...
March 2017: Science Immunology
https://www.readbyqxmd.com/read/28690613/relb-steady-state-migratory-dendritic-cells-control-the-peripheral-pool-of-the-natural-foxp3-regulatory-t-cells
#5
Anja Döhler, Theresa Schneider, Ina Eckert, Eliana Ribechini, Nico Andreas, Marc Riemann, Boris Reizis, Falk Weih, Manfred B Lutz
Thymus-derived natural Foxp3(+) CD4(+) regulatory T cells (nTregs) play a key role in maintaining immune tolerance and preventing autoimmune disease. Several studies indicate that dendritic cells (DCs) are critically involved in the maintenance and proliferation of nTregs. However, the mechanisms how DCs manage to keep the peripheral pool at constant levels remain poorly understood. Here, we describe that the NF-κB/Rel family transcription factor RelB controls the frequencies of steady-state migratory DCs (ssmDCs) in peripheral lymph nodes and their numbers control peripheral nTreg homeostasis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28674001/delineation-of-an-immunosuppressive-gradient-in-hepatocellular-carcinoma-using-high-dimensional-proteomic-and-transcriptomic-analyses
#6
Valerie Chew, Liyun Lai, Lu Pan, Chun Jye Lim, Juntao Li, Raymond Ong, Camillus Chua, Jing Yao Leong, Kiat Hon Lim, Han Chong Toh, Ser Yee Lee, Chung Yip Chan, Brian K P Goh, Alexander Chung, Pierce K H Chow, Salvatore Albani
The recent development of immunotherapy as a cancer treatment has proved effective over recent years, but the precise dynamics between the tumor microenvironment (TME), nontumor microenvironment (NTME), and the systemic immune system remain elusive. Here, we interrogated these compartments in hepatocellular carcinoma (HCC) using high-dimensional proteomic and transcriptomic analyses. By time-of-flight mass cytometry, we found that the TME was enriched in regulatory T cells (Tregs), tissue resident memory CD8(+) T cells (TRMs), resident natural killer cells (NKRs), and tumor-associated macrophages (TAMs)...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28661722/unconventional-or-preset-%C3%AE-%C3%AE-t-cells-evolutionarily-conserved-tissue-resident-t-cells-recognizing-nonpeptidic-ligands
#7
Francois Legoux, Marion Salou, Olivier Lantz
A majority of T cells bearing the αβ T cell receptor (TCR) are specific for peptides bound to polymorphic classical major histocompatibility complex (MHC) molecules. Smaller subsets of T cells are reactive toward various nonpeptidic ligands associated with nonpolymorphic MHC class-Ib (MHC-Ib) molecules. These cells have been termed unconventional for decades, even though only the composite antigen is different from the one seen by classical T cells. Herein, we discuss the identity of these particular T cells in light of the coevolution of their TCR and MHC-Ib restricting elements...
June 29, 2017: Annual Review of Cell and Developmental Biology
https://www.readbyqxmd.com/read/28646160/loss-of-g%C3%AE-i-proteins-impairs-thymocyte-development-disrupts-t-cell-trafficking-and-leads-to-an-expanded-population-of-splenic-cd4-pd-1-cxcr5-t-cells
#8
Il-Young Hwang, Kathleen Harrison, Chung Park, John H Kehrl
Thymocyte and T cell trafficking relies on signals initiated by G-protein coupled receptors. To address the importance of the G-proteins Gαi2 and Gαi3 in thymocyte and T cell function, we developed several mouse models. Gαi2 deficiency in hematopoietic progenitors led to a small thymus, a double negative (DN)1/DN2 thymocyte transition block, and an accumulation of mature single positive (SP) thymocytes. Loss at the double positive (DP) stage of thymocyte development caused an increase in mature cells within the thymus...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645309/herpes-simplex-virus-1-infects-the-olfactory-bulb-shortly-following-ocular-infection-and-exhibits-a-long-term-inflammatory-profile-in-the-form-of-effector-and-hsv-1-specific-t-cells
#9
Chandra M Menendez, Daniel J J Carr
BACKGROUND: Herpes simplex virus 1 (HSV-1) infection can result in a life-threatening condition known as herpes simplex encephalitis (HSE). Trafficking patterns by which the virus reaches the central nervous system (CNS) following ocular infection are unresolved. We evaluated early viral dissemination pathways following ocular infection that involve trafficking to the olfactory bulb (OB). Additionally, we have characterized the capacity of HSV-1 to establish latency within OB tissue and profiled the local T lymphocyte response over the course of the acute infection into latency...
June 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28628092/tissue-resident-memory-features-are-linked-to-the-magnitude-of-cytotoxic-t-cell-responses-in-human-lung-cancer
#10
Anusha-Preethi Ganesan, James Clarke, Oliver Wood, Eva M Garrido-Martin, Serena J Chee, Toby Mellows, Daniela Samaniego-Castruita, Divya Singh, Grégory Seumois, Aiman Alzetani, Edwin Woo, Peter S Friedmann, Emma V King, Gareth J Thomas, Tilman Sanchez-Elsner, Pandurangan Vijayanand, Christian H Ottensmeier
Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3...
August 2017: Nature Immunology
https://www.readbyqxmd.com/read/28620836/sox2-immunity-and-tissue-resident-memory-in-children-and-young-adults-with-glioma
#11
Juan C Vasquez, Anita Huttner, Lin Zhang, Asher Marks, Amy Chan, Joachim M Baehring, Kristopher T Kahle, Kavita M Dhodapkar
Therapies targeting immune checkpoints are effective in tumors with a high mutation burden that express multiple neo-antigens. However, glial tumors including those seen in children carry fewer mutations and there is an unmet need to identify new antigenic targets of anti-tumor immunity. SOX2 is an embryonal stem cell antigen implicated in the biology of glioma initiating cells. Expression of SOX2 by pediatric glial tumors and the capacity of the immune system in these patients to recognize SOX2 has not been previously studied...
June 15, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28599078/non-lesional-atopic-dermatitis-skin-shares-similar-t-cell-clones-with-lesional-tissues
#12
Patrick M Brunner, Ryan O Emerson, Christopher Tipton, Sandra Garcet, Saakshi Khattri, Israel Coats, James G Krueger, Emma Guttman-Yassky
BACKGROUND: Atopic dermatitis (AD) is characterized by robust immune activation. Various T-cell subsets, including Th2/Th22 cells, are increased in lesional and non-lesional skin. However, there is conflicting literature on the diversity of the T-cell receptor (TCR) repertoire in lesional AD, and its relation to non-lesional skin remains unclear. METHODS: We performed high-throughput deep sequencing of the β-TCR repertoire in 29 lesional and 19 non-lesional AD biopsies, compared to 6 healthy control and 6 cutaneous T-cell lymphoma (CTCL) samples from previously published cohorts...
June 9, 2017: Allergy
https://www.readbyqxmd.com/read/28562153/increased-frequencies-of-circulating-and-tumor-resident-v%C3%AE-1-t-cells-in-patients-with-diffuse-large-b-cell-lymphoma
#13
Emilie Reboursiere, Anne-Claire Gac, Anthony Garnier, Véronique Salaun, Oumedaly Reman, Anne-Dominique Pham, Quentin Cabrera, Kathy Khoy, Jean-Pierre Vilque, Christophe Fruchart, Sylvain Chantepie, Hyacinthe Johnson-Ansah, Margaret Macro, Stéphane Cheze, Khaled Benabed, Jean-Baptiste Mear, Xavier Troussard, Gandhi Damaj, Brigitte Le Mauff, Olivier Toutirais
Gamma-delta (γδ) T cells contribute to the innate immune response against cancer. In samples of 20 patients upon DLBCL diagnosis, we found that Vδ1(+) T cells were the major γδ T cell subset in tumors and PBMCs of patients, while Vδ2 T cells were preponderant in PBMCs of healthy subjects. Interestingly, the germinal center (GC) subtype was associated with an increase in Vδ1(+) T cells in tumors, whereas the non-GC subtype was associated with a lower frequency of γδ T cells. While circulating Vδ1(+) T cells of patients or HSs mostly exhibited a naïve phenotype, the majority of tumor Vδ1(+) T cells showed a central memory phenotype...
May 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28539429/bolstering-the-number-and-function-of-hsv-1-specific-cd8-effector-memory-t-cells-and-tissue-resident-memory-t-cells-in-latently-infected-trigeminal-ganglia-reduces-recurrent-ocular-herpes-infection-and-disease
#14
Arif A Khan, Ruchi Srivastava, Aziz A Chentoufi, Elizabeth Kritzer, Sravya Chilukuri, Sumit Garg, David C Yu, Hawa Vahed, Lei Huang, Sabrina A Syed, Julie N Furness, Tien T Tran, Nesburn B Anthony, Christine E McLaren, John Sidney, Alessandro Sette, Randolph J Noelle, Lbachir BenMohamed
HSV type 1 (HSV-1) is a prevalent human pathogen that infects >3.72 billion individuals worldwide and can cause potentially blinding recurrent corneal herpetic disease. HSV-1 establishes latency within sensory neurons of trigeminal ganglia (TG), and TG-resident CD8(+) T cells play a critical role in preventing its reactivation. The repertoire, phenotype, and function of protective CD8(+) T cells are unknown. Bolstering the apparent feeble numbers of CD8(+) T cells in TG remains a challenge for immunotherapeutic strategies...
July 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28537262/induction-of-resident-memory-t-cells-enhances-the-efficacy-of-cancer-vaccine
#15
Mevyn Nizard, Hélène Roussel, Mariana O Diniz, Soumaya Karaki, Thi Tran, Thibault Voron, Estelle Dransart, Federico Sandoval, Marc Riquet, Bastien Rance, Elie Marcheteau, Elizabeth Fabre, Marion Mandavit, Magali Terme, Charlotte Blanc, Jean-Baptiste Escudie, Laure Gibault, Françoise Le Pimpec Barthes, Clemence Granier, Luis C S Ferreira, Cecile Badoual, Ludger Johannes, Eric Tartour
Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in tissue and do not recirculate. Although they are considered as early immune effectors in infectious diseases, their role in cancer immunosurveillance remains unknown. In a preclinical model of head and neck cancer, we show that intranasal vaccination with a mucosal vector, the B subunit of Shiga toxin, induces local Trm and inhibits tumour growth. As Trm do not recirculate, we demonstrate their crucial role in the efficacy of cancer vaccine with parabiosis experiments...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28537249/airway-t-cells-protect-against-rsv-infection-in-the-absence-of-antibody
#16
E Kinnear, L Lambert, J U McDonald, H M Cheeseman, L J Caproni, J S Tregoning
Tissue resident memory T (Trm) cells act as sentinels and early responders to infection. Respiratory syncytial virus (RSV)-specific Trm cells have been detected in the lungs after human RSV infection, but whether they have a protective role is unknown. To dissect the protective function of Trm cells, BALB/c mice were infected with RSV; infected mice developed antigen-specific CD8(+) Trm cells (CD103(+)/CD69(+)) in the lungs and airways. Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice...
May 24, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28533445/lung-cd4-tissue-resident-memory-t-cells-mediate-adaptive-immunity-induced-by-previous-infection-of-mice-with-bordetella-pertussis
#17
Mieszko M Wilk, Alicja Misiak, Róisín M McManus, Aideen C Allen, Marina A Lynch, Kingston H G Mills
Th1 and Th17 cells have an established role in protective immunity to Bordetella pertussis, but this evidence is based largely on peripheral T cells. There is emerging evidence that local tissue-resident memory T (TRM) cells that accumulate in tissue following mucosal infection may be crucial for long-term immunity. In this study, we examined the role of respiratory CD4 TRM cells in immunity to B. pertussis Natural immunity to B. pertussis induced by infection is considered long lasting and effective at preventing reinfection...
May 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#18
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
June 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#19
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28513594/regionally-compartmentalized-resident-memory-t-cells-mediate-naturally-acquired-protection-against-pneumococcal-pneumonia
#20
N Ms Smith, G A Wasserman, F T Coleman, K L Hilliard, K Yamamoto, E Lipsitz, R Malley, H Dooms, M R Jones, L J Quinton, J P Mizgerd
As children age, they become less susceptible to the diverse microbes causing pneumonia. These microbes are pathobionts that infect the respiratory tract multiple times during childhood, generating immunological memory. To elucidate mechanisms of such naturally acquired immune protection against pneumonia, we modeled a relevant immunological history in mice by infecting their airways with mismatched serotypes of Streptococcus pneumoniae (pneumococcus). Previous pneumococcal infections provided protection against a heterotypic, highly virulent pneumococcus, as evidenced by reduced bacterial burdens and long-term sterilizing immunity...
May 17, 2017: Mucosal Immunology
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