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Recent thymic emigrant

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https://www.readbyqxmd.com/read/29722011/end-stage-renal-disease-dialysis-kidney-transplantation-and-their-impact-on-cd4-t-cell-differentiation
#1
Matthias Schaier, Angele Leick, Lorenz Uhlmann, Florian Kälble, Christian Morath, Volker Eckstein, Anthony Ho, Carsten Mueller-Tidow, Stefan Meuer, Karsten Mahnke, Claudia Sommerer, Martin Zeier, Andrea Steinborn
Premature aging of both CD4+ -regulatory- (Tregs) and CD4+ -responder-T-cells (Tresps) in end-stage renal disease (ESRD) patients is expected to affect the success of later kidney transplantation. Both T-cell populations are released from the thymus as inducible co-stimulatory (ICOS+ -) and ICOS- -recent thymic emigrant (RTE)-Tregs/Tresps, which differ primarily in their proliferative capacities. In this study, we analysed the effect of ESRD and subsequent renal replacement therapies on the differentiation of ICOS+ - and ICOS- -RTE-Tregs/Tresps into ICOS+ - or ICOS- -CD31- -Memory-Tregs/Tresps and examined whether diverging pathways affected the suppressive activity of ICOS+ - and ICOS- -Tregs in co-culture with autologous Tresps...
May 2, 2018: Immunology
https://www.readbyqxmd.com/read/29656444/predicting-therapeutic-response-to-fingolimod-treatment-in-multiple-sclerosis-patients
#2
Bibiana Quirant-Sánchez, José V Hervás-García, Aina Teniente-Serra, Luis Brieva, Ester Moral-Torres, Antonio Cano, Elvira Munteis, María J Mansilla, Silvia Presas-Rodriguez, Juan Navarro-Barriuso, Cristina Ramo-Tello, Eva M Martínez-Cáceres
AIMS: Fingolimod, an orally active immunomodulatory drug for relapsing-remitting multiple sclerosis (RRMS), sequesters T cells in lymph nodes through functional antagonism of the sphingosine-1-phosphate receptor, reducing the number of potential autoreactive cells that migrate to the central nervous system. However, not all RRMS patients respond to this therapy. Our aim was to test the hypothesis that by immune-monitoring RRMS patient's leukocyte subpopulations it is possible to find biomarkers associated with clinical response to fingolimod...
April 15, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29518102/expression-of-pd-1-and-tim-3-markers-of-t-cell-exhaustion-is-associated-with-cd4-dynamics-during-the-course-of-untreated-and-treated-hiv-infection
#3
Norma Rallón, Marcial García, Javier García-Samaniego, Alfonso Cabello, Beatriz Álvarez, Clara Restrepo, Sara Nistal, Miguel Górgolas, José M Benito
INTRODUCTION: T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection. PATIENTS AND METHODS: 96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31-60] months...
2018: PloS One
https://www.readbyqxmd.com/read/29517845/major-features-of-immunesenescence-including-reduced-thymic-output-are-ameliorated-by-high-levels-of-physical-activity-in-adulthood
#4
Niharika Arora Duggal, Ross D Pollock, Norman R Lazarus, Stephen Harridge, Janet M Lord
It is widely accepted that aging is accompanied by remodelling of the immune system including thymic atrophy and increased frequency of senescent T cells, leading to immune compromise. However, physical activity, which influences immunity but declines dramatically with age, is not considered in this literature. We assessed immune profiles in 125 adults (55-79 years) who had maintained a high level of physical activity (cycling) for much of their adult lives, 75 age-matched older adults and 55 young adults not involved in regular exercise...
April 2018: Aging Cell
https://www.readbyqxmd.com/read/29490663/class-modeling-analysis-reveals-t-cell-homeostasis-disturbances-involved-in-loss-of-immune-control-in-elite-controllers
#5
José M Benito, María C Ortiz, Agathe León, Luis A Sarabia, José M Ligos, María Montoya, Marcial Garcia, Ezequiel Ruiz-Mateos, Rosario Palacios, Alfonso Cabello, Clara Restrepo, Carmen Rodriguez, Jorge Del Romero, Manuel Leal, María A Muñoz-Fernández, José Alcamí, Felipe García, Miguel Górgolas, Norma Rallón
BACKGROUND: Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. Discovering perturbations in immunological parameters could help our understanding of the mechanisms that may be operating in those patients experiencing loss of immunological control. METHODS: A case-control study was performed to evaluate if alterations in different T-cell homeostatic parameters can predict CD4 T-cell loss in ECs by comparing data from EC patients showing significant CD4 decline (cases) and EC patients showing stable CD4 counts (controls)...
February 28, 2018: BMC Medicine
https://www.readbyqxmd.com/read/29416537/prior-to-peripheral-tolerance-newly-generated-cd4-t-cells-maintain-dangerous-autoimmune-potential-fas-and-perforin-independent-autoimmunity-controlled-by-programmed-death-1
#6
Kristofor K Ellestad, Govindarajan Thangavelu, Yohannes Haile, Jiaxin Lin, Louis Boon, Colin C Anderson
Lymphopenia can result from various factors, including viral infections, clinical interventions, or as a normal property of the fetal/neonatal period. T cells in a lymphopenic environment undergo lymphopenia-induced proliferation (LIP) to fill the available "niche" as defined by peptide-MHC and homeostatic cytokine resources. We recently reported systemic autoimmunity following reconstitution of the lymphoid compartment of Rag1-/- mice with PD-1-/- hematopoietic stem cells or by transfer of thymocytes, but not splenocytes, suggesting that programmed death-1 (PD-1) plays a crucial role in controlling recent thymic emigrants (RTE) and preventing autoimmunity upon their LIP...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29366602/treg-specific-deletion-of-nkap-results-in-severe-systemic-autoimmunity-due-to-peripheral-loss-of-tregs
#7
Barsha Dash, Michael J Shapiro, Ji Young Chung, Sinibaldo Romero Arocha, Virginia Smith Shapiro
Regulatory T cells are critical for the generation and maintenance of peripheral tolerance. Conditional deletion of the transcriptional repressor NKAP in Tregs using Foxp3-YFP-cre NKAP conditional knockout mice causes aggressive autoimmunity characterized by thymic atrophy, lymphadenopathy, peripheral T cell activation, generation of autoantibodies, immune infiltration into several organs, and crusty skin at 3 weeks of age, similar to that of "scurfy" Foxp3-mutant mice. While Treg development in the thymus proceeds normally in the absence of NKAP, there is a severe loss of thymically-derived Tregs in the periphery...
May 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29365321/immune-rebound-associates-with-a-favorable-clinical-response-to-autologous-hsct-in-systemic-sclerosis-patients
#8
Lucas C M Arruda, Kelen C R Malmegrim, João R Lima-Júnior, Emmanuel Clave, Juliana B E Dias, Daniela A Moraes, Corinne Douay, Isabelle Fournier, Hélène Moins-Teisserenc, Antônio José Alberdi, Dimas T Covas, Belinda P Simões, Pauline Lansiaux, Antoine Toubert, Maria Carolina Oliveira
To evaluate the immunological mechanisms associated with clinical outcomes after autologous hematopoietic stem cell transplantation (AHSCT), focusing on regulatory T- (Treg) and B- (Breg) cell immune reconstitution, 31 systemic sclerosis (SSc) patients underwent simultaneous clinical and immunological evaluations over 36-month posttransplantation follow-up. Patients were retrospectively grouped into responders (n = 25) and nonresponders (n = 6), according to clinical response after AHSCT. Thymic function and B-cell neogenesis were respectively assessed by quantification of DNA excision circles generated during T- and B-cell receptor rearrangements...
January 23, 2018: Blood Advances
https://www.readbyqxmd.com/read/29288207/newly-generated-cd4-t-cells-acquire-metabolic-quiescence-after-thymic-egress
#9
Shusong Zhang, Xinwei Zhang, Ke Wang, Xi Xu, Mingyang Li, Jun Zhang, Yan Zhang, Jie Hao, Xiuyuan Sun, Yingyu Chen, Xiaohui Liu, Yingjun Chang, Rong Jin, Hounan Wu, Qing Ge
Mature naive T cells circulate through the secondary lymphoid organs in an actively enforced quiescent state. Impaired cell survival and cell functions could be found when T cells have defects in quiescence. One of the key features of T cell quiescence is low basal metabolic activity. It remains unclear at which developmental stage T cells acquire this metabolic quiescence. We compared mitochondria among CD4 single-positive (SP) T cells in the thymus, CD4+ recent thymic emigrants (RTEs), and mature naive T cells in the periphery...
February 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29163492/t-cell-composition-of-the-lymph-node-is-associated-with-the-risk-for-early-rejection-after-renal-transplantation
#10
Burç Dedeoglu, Nicolle H R Litjens, Annelies E de Weerd, Frank Jmf Dor, Mariska Klepper, Derek Reijerkerk, Carla C Baan, Michiel G H Betjes
Background: The T-cell composition within the lymph node (LN) of end-stage renal disease (ESRD) patients differs from the composition within the circulation. Activation of the alloreactive T-cell response within secondary lymphoid organs is important after organ transplantation. However, to date no data are present on LN T-cell subsets and the risk for acute rejection after kidney transplantation. Methods: T cells from LNs of ESRD patients were analyzed for frequency of recent thymic emigrants, relative telomere length, expression of differentiation markers, and were related to the development of early acute rejection (EAR), occurring within 3 months after renal transplantation (RT)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29160947/thymic-function-is-a-major-determinant-of-onset-of-antibody-mediated-rejection-in-heart-transplantation
#11
A Sannier, N Stroumza, G Caligiuri, M Le Borgne-Moynier, F Andreata, J Senemaud, L Louedec, G Even, A T Gaston, C Deschildre, A Couvelard, P Ou, R Cheynier, P Nataf, R Dorent, A Nicoletti
Thymic function decreases progressively with age but may be boosted in certain circumstances. We questioned whether heart transplantation was such a situation and whether thymic function was related to the onset of rejection. Twenty-eight antithymocyte globulin-treated heart transplant recipients were included. Patients diagnosed for an antibody-mediated rejection on endomyocardial biopsy had a higher proportion of circulating recent thymic emigrant CD4+ T cells and T cell receptor excision circle levels than other transplanted subjects...
April 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29136317/il-7-receptor-heterogeneity-as-a-mechanism-for-repertoire-change-during-postdepletional-homeostatic-proliferation-and-its-relation-to-costimulation-blockade-resistant-rejection
#12
He Xu, Victoria A Bendersky, Todd V Brennan, Jaclyn R Espinosa, Allan D Kirk
Kidney transplant patients treated with belatacept without depletional induction experience higher rates of acute rejection compared to patients treated with conventional immunosuppression. Costimulation blockade-resistant rejection (CoBRR) is associated with terminally differentiated T cells. Alemtuzumab induction and belatacept/sirolimus immunotherapy effectively prevent CoBRR. We hypothesized that cells in late phases of differentiation would be selectively less capable than more naive phenotypes of repopulating postdepletion, providing a potential mechanism by which lymphocyte depletion and repopulation could reduce the risk of CoBRR...
November 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28941751/immune-reconstitution-with-two-different-rabbit-polyclonal-anti-thymocytes-globulins
#13
Jamal Bamoulid, Thomas Crepin, Emilie Gaiffe, Caroline Laheurte, Bruno Moulin, Luc Frimat, Philippe Rieu, Christiane Mousson, Antoine Durrbach, Anne-Elisabeth Heng, Jean-Michel Rebibou, Philippe Saas, Cécile Courivaud, Didier Ducloux
Broad T cell depletion by polyclonal anti-thymocyte globulins (ATG) has been used for many years as a part of immunosuppressive treatment in transplantation. Currently, two different ATG are used in clinical practice, Thymoglobulin and Grafalon. Due to differences in the immunization source, these products contain different specificities and quantity of antibodies. These differences may have clinical consequences. We conducted a nested study in a large prospective multicentric cohort of kidney transplant to determine whether Grafalon-treated and Thymoglobulin-treated patients experience different lymphocyte reconstitution and clinical outcomes...
September 20, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28937406/tolerance-in-xenotransplantation
#14
REVIEW
Kazuhiko Yamada, Megan Sykes, David H Sachs
PURPOSE OF REVIEW: This review describes recent progress in tolerance-inducing strategies across xenogeneic immunological barriers as well as the potential benefit of a tolerance strategy for islets and kidney xenotransplantation. RECENT FINDINGS: Using advanced gene editing technologies, xenotransplantation from multitransgenic alpha-1,3-galactosyltransferase knockout pigs has demonstrated marked prolongation of renal xenograft survival, ranging from days to greater than several months for life-supporting kidneys, and more than 2 years in a heterotopic nonlife-supporting cardiac xenograft model...
December 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28821585/a-coronin-1-dependent-decision-switch-in-juvenile-mice-determines-the-population-of-the-peripheral-naive-t-cell-compartment
#15
Mathias Jakob Lang, Mayumi Mori, Julie Ruer-Laventie, Jean Pieters
Following thymic maturation, T cells egress as recent thymic emigrants to peripheral lymphoid organs where they undergo an additional maturation step to mature naive T cells that circulate through secondary lymphoid organs ready to be activated upon pathogenic challenges. Thymic maturation and peripheral T cell survival depend on several signaling cascades, but whether a dedicated mechanism exists that exclusively regulates homeostasis of mature naive T cells without affecting thymocytes and/or recent thymic emigrants remains unknown...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28814669/neonatal-and-adult-recent-thymic-emigrants-produce-il-8-and-express-complement-receptors-cr1-and-cr2
#16
Marcin L Pekalski, Arcadio Rubio García, Ricardo C Ferreira, Daniel B Rainbow, Deborah J Smyth, Meghavi Mashar, Jane Brady, Natalia Savinykh, Xaquin Castro Dopico, Sumiyya Mahmood, Simon Duley, Helen E Stevens, Neil M Walker, Antony J Cutler, Frank Waldron-Lynch, David B Dunger, Claire Shannon-Lowe, Alasdair J Coles, Joanne L Jones, Chris Wallace, John A Todd, Linda S Wicker
The maintenance of peripheral naive T lymphocytes in humans is dependent on their homeostatic division, not continuing emigration from the thymus, which undergoes involution with age. However, postthymic maintenance of naive T cells is still poorly understood. Previously we reported that recent thymic emigrants (RTEs) are contained in CD31+CD25- naive T cells as defined by their levels of signal joint T cell receptor rearrangement excision circles (sjTRECs). Here, by differential gene expression analysis followed by protein expression and functional studies, we define that the naive T cells having divided the least since thymic emigration express complement receptors (CR1 and CR2) known to bind complement C3b- and C3d-decorated microbial products and, following activation, produce IL-8 (CXCL8), a major chemoattractant for neutrophils in bacterial defense...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28754679/adaptive-from-innate-human-ifn-%C3%AE-cd4-t-cells-can-arise-directly-from-cxcl8-producing-recent-thymic-emigrants-in-babies-and-adults
#17
Abhishek Das, Kevin Rouault-Pierre, Shraddha Kamdar, Iria Gomez-Tourino, Kristie Wood, Ian Donaldson, Charles A Mein, Dominique Bonnet, Adrian C Hayday, Deena L Gibbons
We recently demonstrated that the major effector function of neonatal CD4+ T cells is to produce CXCL8, a prototypic cytokine of innate immune cells. In this article, we show that CXCL8 expression, prior to proliferation, is common in newly arising T cells (so-called "recent thymic emigrants") in adults, as well as in babies. This effector potential is acquired in the human thymus, prior to TCR signaling, but rather than describing end-stage differentiation, such cells, whether isolated from neonates or adults, can further differentiate into IFN-γ-producing CD4+ T cells...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28722017/the-role-of-age-related-t-cell-differentiation-in-patients-with-renal-replacement-therapy
#18
Matthias Schaier, Angele Leick, Lorenz Uhlmann, Florian Kälble, Volker Eckstein, Anthony Ho, Stefan Meuer, Karsten Mahnke, Claudia Sommerer, Martin Zeier, Andrea Steinborn
Dialysis patients have deficiencies regarding the generation of immune responses and show an increased susceptibility for infections. Persisting uremic conditions are made responsible for the increased aging of their immune system. In this study, we analyzed whether age-related differences in the differentiation of both recent-thymic-emigrant-(RTE)-regulatory (Tregs) and RTE-responder T cells (Tresps) into CD31- -memory Tregs/Tresps led to differences in the suppressive activity of naive and memory Tregs on autologous Tresps between healthy volunteers and dialysis patients...
November 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28694386/a-type-2-cytokine-axis-for-thymus-emigration
#19
Andrea J White, Song Baik, Sonia M Parnell, Amanda M Holland, Frank Brombacher, William E Jenkinson, Graham Anderson
In the thymus, stromal microenvironments support a developmental program that generates mature T cells ready for thymic exit. The cellular and molecular specialization within thymic stromal cells that enables their regulation of specific stages of thymocyte development is poorly understood. Here, we show the thymic microenvironment expresses the type 2 IL-4R complex and is functionally responsive to its known ligands, IL-4 and IL-13. Absence of IL-4Rα limits thymocyte emigration, leading to an intrathymic accumulation of mature thymocytes within medullary perivascular spaces and reduced numbers of recent thymic emigrants...
August 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28674683/infusion-of-sibling-marrow-in-a-patient-with-purine-nucleoside-phosphorylase-deficiency-leads-to-split-mixed-donor-chimerism-and-normal-immunity
#20
Laura Yeates, Mary A Slatter, Andrew R Gennery
Purine nucleoside phosphorylase (PNP) deficiency, a rare autosomal recessive metabolic disease causes combined immunodeficiency and developmental delay, hypotonia, and spasticity. Patients present with recurrent infections associated with T-lymphocytopenia, characteristically presenting later than patients with classical severe combined immunodeficiency (SCID). PNP, with adenosine deaminase (ADA), is part of the purine salvage pathway. The only curative therapy is hematopoietic stem cell transplantation. Myeloablative conditioning is recommended to prevent rejection caused by residual immune function...
2017: Frontiers in Pediatrics
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