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https://www.readbyqxmd.com/read/28647348/pivotal-role-of-lesional-and-perilesional-t-b-lymphocytes-in-pemphigus-pathogenesis
#1
Huijie Yuan, Shengru Zhou, Zhicui Liu, Weiting Cong, Xiaochun Fei, Weihong Zeng, Haiqin Zhu, Renchao Xu, Ying Wang, Jie Zheng, Meng Pan
Pemphigus is a skin and mucosal membrane-targeting autoimmune bullous disease. Previous studies have demonstrated that circulating anti-desmoglein1/3 antibodies are pathogenic and mediate blister formation. However, the role of infiltrated immune cells in the lesional skin has not been fully investigated. In this study we showed that there existed a large number of B, T lymphocytes and plasma cells in the skin lesions by immunohistochemistry and immunofluorescence staining. In addition, a significantly increased number of Dsg1 and Dsg3-specific B cells could be identified by flow cytometric analysis or ELISPOT assay...
June 21, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28646040/il-23-limits-the-production-of-il-2-and-promotes-autoimmunity-in-lupus
#2
Hong Dai, Fan He, George C Tsokos, Vasileios C Kyttaris
The IL-23/IL-17 pathway is important in multiple autoimmune diseases, but its effect on lupus pathology remains unclear, with opposing trials in murine models of the disease. In this study, we show a disease activity-related upregulation of serum IL-23 and IL-23 receptor in patients with systemic lupus erythematosus (SLE) as compared with healthy controls. When added in SLE T cell in vitro cultures, IL-23 induced IL-17 and limited IL-2 production, whereas T follicular helper and double negative (DN) T cells significantly expanded...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28643847/ncr1-deficiency-diminishes-the-generation-of-protective-murine-cytomegalovirus-antibodies-by-limiting-follicular-helper-t-cell-maturation
#3
Antonija Miletic, Maja Lenartic, Branka Popovic, Ilija Brizic, Tihana Trsan, Karmela Miklic, Ofer Mandelboim, Astrid Krmpotic, Stipan Jonjic
NKp46/NCR1 is an activating NK-cell receptor implicated in the control of various viral and bacterial infections. Recent findings also suggest that it plays a role in shaping the adaptive immune response to pathogens. Using NCR1-deficient (NCR1(gfp/gfp) ) mice we provide evidence for the role of NCR1 in antibody response to mouse cytomegalovirus infection (MCMV). The absence of NCR1 resulted in impaired maturation, function and NK-cell migration to regional lymph nodes. In addition, CD4(+) T-cell activation and follicular helper T-cell (Tfh) generation were reduced, leading to inferior germinal center (GC) B-cell maturation...
June 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28639391/an-investigation-of-the-relationship-between-recurrent-spontaneous-abortion-and-memory-t-follicular-helper-cells
#4
Xiaorui Luan, Xiaomin Kang, Weiping Li, Qian Dong
PROBLEM: Immune tolerance with respect to a semi-allogeneic fetus plays a key role in the establishment of a pregnancy. Memory T follicular helper (Tfh) cells have a central role in the regulation of the adaptive immune response. Much of our knowledge of memory Tfh cells' function comes from immune-related diseases. However, the true physiological characteristics of memory Tfh cells and their mode of action in pregnancy remain unclear. METHODS OF STUDY: Deciduas and blood were obtained from 25 recurrent spontaneous abortion (RSA) patients undergoing surgical abortion and 19 normal women in early pregnancy undergoing elective termination...
June 21, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28637884/vaccination-establishes-clonal-relatives-of-germinal-center-t-cells-in-the-blood-of-humans
#5
Antje Heit, Frank Schmitz, Sarah Gerdts, Britta Flach, Miranda S Moore, Jonathan A Perkins, Harlan S Robins, Alan Aderem, Paul Spearman, Georgia D Tomaras, Stephen C De Rosa, M Juliana McElrath
Germinal center T follicular helper cells (GCTfh) in lymphatic tissue are critical for B cell differentiation and protective antibody induction, but whether GCTfh establish clonal derivatives as circulating memory T cells is less understood. Here, we used markers expressed on GCTfh, CXCR5, PD1, and ICOS, to identify potential circulating CXCR5(+)CD4(+) Tfh-like cells (cTfh) in humans, and investigated their functional phenotypes, diversity, and ontogeny in paired donor blood and tonsils, and in blood after vaccination...
June 21, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28637095/selective-cd28-blockade-results-in-superior-inhibition-of-donor-specific-t-follicular-helper-cell-and-antibody-responses-relative-to-ctla-4-ig
#6
I R Badell, G M La Muraglia, D Liu, M E Wagener, G Ding, M L Ford
Donor-specific antibodies (DSA) are a barrier to improved long-term outcomes following kidney transplantation. Costimulation blockade with CTLA-4-Ig has shown promise as a potential therapeutic strategy to control DSA. T follicular helper (Tfh) cells, a subset of CD4(+) T cells required for optimum antibody production, are reliant on the CD28 costimulatory pathway. We have previously shown that selective CD28 blockade leads to superior allograft survival through improved control of CD8(+) T cells relative to CTLA-4-Ig, but the impact of CD28-specific blockade on CD4(+) Tfh cells is unknown...
June 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28636997/an-optimized-hmgb1-expressed-by-recombinant-rabies-virus-enhances-immunogenicity-through-activation-of-dendritic-cells-in-mice
#7
Zhao Wang, Qian Liang, Yajing Zhang, Jie Yang, Mingming Li, Kunlun Wang, Min Cui, Huanchun Chen, Zhen F Fu, Ling Zhao, Ming Zhou
Rabies remains an important public health threat, killing approximately 59,000 people worldwide annually, most of which are from the developing countries of Africa and Asia where dog rabies are endemic. Therefore, developing an affordable and efficacious vaccine for dog-mediated rabies control is needful in these countries. Our previous studies indicated that over-expression of granulocyte-macrophage colony stimulating factor (GM-CSF) or macrophage inflammatory protein-1 (MIP-1α or CCL3) by recombinant rabies virus (rRABV) could enhance the immunogenicity by activating dendritic cells (DCs)...
June 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28631561/proinflammatory-follicular-helper-t-cells-promote-immunoglobulin-g-secretion-suppress-regulatory-b-cell-development-and-correlate-with-worse-clinical-outcomes-in-gastric-cancer
#8
Hong Zhang, Rongxi Yue, Pengfei Zhao, Xuetao Yu, Junguo Li, Guoqing Ma, Jiahong Tang, Lixin Zhang, Liying Feng, Lidong Sun, Zongchang Song, Chunliang Guo, Ning Wang
Gastric cancer is one of the most common and aggressive malignancies. Both bacterial virulence factors and host chronic inflammation are thought to promote gastric cancer development. In this study, we investigated the potential involvement of follicular helper T cells in gastric cancer. Functions of follicular helper T subsets were examined in Helicobacter pylori-infected gastric cancer patients and H. pylori-infected but asymptomatic individuals. We found that the follicular helper T cells in gastric cancer individuals were skewed toward the Th1 and Th17 subsets compared to those in H...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28628673/multiple-tolerance-defects-contribute-to-the-breach-of-b-cell-tolerance-in-new-zealand-black-chromosome-1-congenic-mice
#9
Nan-Hua Chang, Kieran P Manion, Christina Loh, Evelyn Pau, Yuriy Baglaenko, Joan E Wither
Lupus is characterized by a loss of B cell tolerance leading to autoantibody production. In this study, we explored the mechanisms underlying this loss of tolerance using B6 congenic mice with an interval from New Zealand Black chromosome 1 (denoted c1(96-100)) sufficient for anti-nuclear antibody production. Transgenes for soluble hen egg white lysozyme (sHEL) and anti-HEL immunoglobulin were crossed onto this background and various tolerance mechanisms examined. We found that c1(96-100) mice produced increased levels of IgM and IgG anti-HEL antibodies compared to B6 mice and had higher proportions of germinal center B cells and long-lived plasma cells, suggesting a germinal center-dependent breach of B cell anergy...
2017: PloS One
https://www.readbyqxmd.com/read/28628194/signals-that-drive-t-follicular-helper-cell-formation
#10
REVIEW
Louise M C Webb, Michelle A Linterman
T follicular helper (TFH) cells are a distinct type of CD4+ T cell specialized in providing help to B cells during the germinal center (GC) reaction. As such, they are critical determinants of the quality of an antibody response following antigen challenge. Excessive production of TFH cells can result in autoimmunity whilst too few can result in inadequate protection from infection. Hence, their differentiation and maintenance must be tightly regulated to ensure appropriate, but limited, help to B cells. Unlike the majority of other CD4+ T cell subsets, TFH cell differentiation occurs in three phases defined by their anatomical location...
June 19, 2017: Immunology
https://www.readbyqxmd.com/read/28622456/elevated-ccl25-and-ccr9-expressing-t-helper-cells-in-salivary-glands-of-primary-sj%C3%A3-gren-s-syndrome-patients-potential-new-axis-in-lymphoid-neogenesis
#11
Sofie L M Blokland, Maarten R Hillen, Aike A Kruize, Stephan Meller, Bernhard Homey, Glennda M Smithson, Timothy R D J Radstake, Joel A G van Roon
Introduction T follicular helper (Tfh)-cells play a critical role in germinal center formation and B-cell activation, both hallmarks of primary Sjögren's syndrome (pSS). CCR9-expressing Th-cells have "Tfh-like" characteristics and are increased at mucosa-associated sites in several inflammatory conditions. Because of their unique characteristics and limited evaluation we investigated the local and systemic CCL25/CCR9-axis in pSS. Methods CCL25 protein and mRNA levels and CCR9+ Th-cells were assessed in labial salivary glands (LSG) of pSS and non-Sjögren's sicca (nSS) patients and their correlation with inflammatory and clinical parameters was evaluated...
June 16, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28620653/successive-annual-influenza-vaccination-induces-a-recurrent-oligoclonotypic-memory-response-in-circulating-t-follicular-helper-cells
#12
Ramin Sedaghat Herati, Alexander Muselman, Laura Vella, Bertram Bengsch, Kaela Parkhouse, Daniel Del Alcazar, Jonathan Kotzin, Susan A Doyle, Pablo Tebas, Scott E Hensley, Laura F Su, Kenneth E Schmader, E John Wherry
T follicular helper (Tfh) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population of CD4 T cells, termed cTfh, have similarity to lymphoid Tfh, can provide B cell help, and responded to influenza vaccination. However, it is unclear whether human vaccination-induced cTfh respond in an antigen-specific manner and whether they form long-lasting memory. Here, we identified a cTfh population that expressed multiple T cell activation markers and could be readily identified by coexpression of ICOS and CD38...
February 2017: Science Immunology
https://www.readbyqxmd.com/read/28620390/belatacept-does-not-inhibit-follicular-t-cell-dependent-b-cell-differentiation-in-kidney-transplantation
#13
Gretchen N de Graav, Dennis A Hesselink, Marjolein Dieterich, Rens Kraaijeveld, Wenda Verschoor, Dave L Roelen, Nicolle H R Litjens, Anita S Chong, Willem Weimar, Carla C Baan
Humoral alloreactivity has been recognized as a common cause of kidney transplant dysfunction. B-cell activation, differentiation, and antibody production are dependent on IL-21(+)CXCR5(+)follicular T-helper (Tfh) cells. Here, we studied whether belatacept, an inhibitor of the costimulatory CD28-CD80/86-pathway, interrupts the crosstalk between Tfh- and B-cells more efficiently than the calcineurin inhibitor tacrolimus. The suppressive effects of belatacept and tacrolimus on donor antigen-driven Tfh-B-cell interaction were functionally studied in peripheral blood mononuclear cells from 40 kidney transplant patients randomized to a belatacept- or tacrolimus-based immunosuppressive regimen...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28620380/human-immunodeficiency-virus-playing-hide-and-seek-understanding-the-tfh-cell-reservoir-and-proposing-strategies-to-overcome-the-follicle-sanctuary
#14
REVIEW
Yew Ann Leong, Anurag Atnerkar, Di Yu
Human immunodeficiency virus (HIV) infects millions of people worldwide, and new cases continue to emerge. Once infected, the virus cannot be cleared by the immune system and causes acquired immunodeficiency syndrome. Combination antiretroviral therapeutic regimen effectively suppresses viral replication and halts disease progression. The treatment, however, does not eliminate the virus-infected cells, and interruption of treatment inevitably leads to viral rebound. The rebound virus originates from a group of virus-infected cells referred to as the cellular reservoir of HIV...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28617936/t-follicular-regulatory-cells-in-mice-and-men
#15
REVIEW
Ana Raquel Maceiras, Valter R Fonseca, Ana Agua-Doce, Luis Graca
It has long been known that CD4 T cells are necessary to provide help to B cells, triggering a germinal center (GC) reaction where affinity maturation and isotype switching occurs. However, the nature of the dedicated CD4 helper T cells, known as T follicular helper (Tfh), was only recently described. Here, we review the biology and function of the recently described T follicular regulatory (Tfr) cells, another CD4 T cell population also found within GCs but with regulatory function and characteristics. Tfr cells have been identified in mice and humans as simultaneously, presenting simultaneously characteristics of T follicular cells (namely CXCR5 expression) and regulatory T cells (including Foxp3 expression)...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28615202/follicular-regulatory-t-cells-are-highly-permissive-to-r5-tropic-hiv-1
#16
Shannon M Miller, Brodie Miles, Kejun Guo, Joy Folkvord, Amie L Meditz, Martin D McCarter, David N Levy, Samantha MaWhinney, Mario L Santiago, Elizabeth Connick
Follicular regulatory T cells (TFR) are a subset of CD4+ T cells in secondary lymphoid follicles. TFR were previously included in the follicular helper T cell (TFH) subset, which are highly permissive to HIV-1. The permissivity of TFR to HIV-1 is unknown. We find TFR are more permissive than TFH to R5-tropic HIV-1 ex vivo TFR expressed more CCR5 and CD4, and supported higher frequencies of viral fusion. Differences in Ki67 expression correlated with HIV-1 replication. Inhibiting cellular proliferation reduced Ki67 expression and HIV-1 replication...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28614794/an-activated-th17-prone-t-cell-subset-involved-in-chronic-graft-versus-host-disease-sensitive-to-pharmacological-inhibition
#17
Edouard Forcade, Katelyn Paz, Ryan Flynn, Brad Griesenauer, Tohti Amet, Wei Li, Liangyi Liu, Giorgos Bakoyannis, Di Jiang, Hong Wei Chu, Mercedes Lobera, Jianfei Yang, David S Wilkes, Jing Du, Kate Gartlan, Geoffrey R Hill, Kelli Pa MacDonald, Eduardo L Espada, Patrick Blanco, Jonathan S Serody, John Koreth, Corey S Cutler, Joseph H Antin, Robert J Soiffer, Jerome Ritz, Sophie Paczesny, Bruce R Blazar
Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic stem cell transplantation requiring novel therapies. CD146 and CCR5 are expressed by activated T cells and associated with increased T cell migration capacity and Th17 polarization. We performed a multiparametric flow cytometry analysis in a cohort of 40 HSCT patients together with a cGvHD murine model to understand the role of CD146-expressing subsets. We observed an increased frequency of CD146+ CD4 T cells in the 20 patients with active cGvHD with enhanced RORγt expression...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28611626/angioimmunoblastic-t-cell-lymphoma-mimicking-drug-reaction-with-eosinophilia-and-systemic-symptoms-dress-syndrome
#18
Joanna Mangana, Emmanuella Guenova, Katrin Kerl, Mirjana Urosevic-Maiwald, Valerie C Amann, Cornelia Bayard, Reinhard Dummer, Lars E French
Angioimmunoblastic T-cell lymphoma (AITCL) is a rare, aggressive lymphoma which derives from follicular helper T cells, commonly affecting the elderly population. It accounts for 2% of all non-Hodgkin lymphomas, with a reported 5-year overall survival rate of less than 30%. Very often, the clinical picture of AITCL encompasses systemic symptoms such as generalized lymphadenopathy, hepatosplenomegaly, skin rash, anemia, and polyclonal hypergammaglobulinemia. Here we report on the case of a female patient who presented with clinical features resembling drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) prior to the definitive diagnosis of AITCL...
January 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28605013/the-strength-of-bcr-signaling-shapes-terminal-development-of-follicular-helper-t-cells-in-mice
#19
Antoine Sacquin, Mylène Gador, Nicolas Fazilleau
Antibody production is key for effective immune response and relies on follicular helper T (Tfh) cells. B cell-Tfh cell interactions result either in an extra-follicular low affinity B-cell response or in germinal center reactions producing high-affinity memory B cells and long-lived plasma cells. As Tfh cells influence B-cell commitment, it also became clear that B cells influence these interactions in ways that still remain unresolved. We observed that strong BCR signals decreased Tfh-cell differentiation in vitro, which correlated with decreased expression of ICOS-L at the surface of stimulated B cells...
June 12, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28604718/the-transcription-factor-runx3-guards-cytotoxic-cd8-effector-t-cells-against-deviation-towards-follicular-helper-t-cell-lineage
#20
Qiang Shan, Zhouhao Zeng, Shaojun Xing, Fengyin Li, Stacey M Hartwig, Jodi A Gullicksrud, Samarchith P Kurup, Natalija Van Braeckel-Budimir, Yao Su, Matthew D Martin, Steven M Varga, Ichiro Taniuchi, John T Harty, Weiqun Peng, Vladimir P Badovinac, Hai-Hui Xue
Activated CD8(+) T cells differentiate into cytotoxic effector (TEFF) cells that eliminate target cells. How TEFF cell identity is established and maintained is not fully understood. We found that Runx3 deficiency limited clonal expansion and impaired upregulation of cytotoxic molecules in TEFF cells. Runx3-deficient CD8(+) TEFF cells aberrantly upregulated genes characteristic of follicular helper T (TFH) cell lineage, including Bcl6, Tcf7 and Cxcr5. Mechanistically, the Runx3-CBFβ transcription factor complex deployed H3K27me3 to Bcl6 and Tcf7 genes to suppress the TFH program...
June 12, 2017: Nature Immunology
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