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Recent thymic emigrants

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https://www.readbyqxmd.com/read/28722017/the-role-of-age-related-t-cell-differentiation-in-patients-with-renal-replacement-therapy
#1
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 naïve and memory Tregs on autologous Tresps between healthy volunteers and dialysis patients...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28694386/a-type-2-cytokine-axis-for-thymus-emigration
#2
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...
July 10, 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
#3
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
https://www.readbyqxmd.com/read/28607754/lymphocyte-reconstitution-following-autologous-stem-cell-transplantation-for-progressive-ms
#4
G Cull, D Hall, M J Fabis-Pedrini, W M Carroll, L Forster, F Robins, R Ghassemifar, C Crosbie, S Walters, I James, B Augustson, A K Kermode
BACKGROUND: Autologous stem cell transplantation (ASCT) for progressive multiple sclerosis (MS) may reset the immune repertoire. OBJECTIVE: The objective of this paper is to analyse lymphocyte recovery in patients with progressive MS treated with ASCT. METHODS: Patients with progressive MS not responding to conventional treatment underwent ASCT following conditioning with high-dose cyclophosphamide and antithymocyte globulin. Lymphocyte subset analysis was performed before ASCT and for two years following ASCT...
January 2017: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/28542701/two-separate-effects-contribute-to-regulatory-t-cell-defect-in-sle-patients-and-their-unaffected-relatives
#5
Nuno Costa, Oriana Marques, Sandra I Godinho, Cláudia Carvalho, Barbara Leal, Ana M Figueiredo, Carlos Vasconcelos, António Marinho, Maria F Moraes-Fontes, António Gomes da Costa, Cristina Ponte, Raquel Campanilho-Marques, Telma Cóias, Ana R Martins, João F Viana, Margarida Lima, Berta Martins, Constantin Fesel
FOXP3(+) regulatory T-cells (Tregs) are functionally deficient in Systemic Lupus Erythematosus (SLE), characterized by reduced surface CD25 (the IL-2 receptor alpha chain). Low-dose IL-2 therapy is a promising current approach to correct this defect. To elucidate the origins of the SLE Treg phenotype, we studied its role through developmentally defined Treg subsets in 45 SLE patients, 103 SLE-unaffected first-degree relatives and 61 unrelated healthy control subjects, and genetic association with the CD25-encoding IL2RA locus...
May 24, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28532344/pre-transplantation-thymic-function-is-associated-with-the-risk-of-acute-graft-versus-host-disease-and-cytomegalovirus-viremia-after-allogeneic-hematopoietic-stem-cell-transplantation
#6
Xin Yang, Yuanxin Sun, Sudong Zhang, Hui Yang, Jialin Wei, Yi He, Donglin Yang, Erlie Jiang, Mingzhe Han, Xuemei Qin, Sizhou Feng
OBJECTIVES: To analyze the kinetics of T-cell subsets and thymic function reconstitution after allogeneic hematopoietic stem cell transplantation (AHSCT); to determine whether sjTREC (signal joint TCR rearrangement excision circle) and CD31-positive recent thymic emigrant (CD31 + RTE) are correlated with acute graft versus host disease (aGVHD) or CMV (cytomegalovirus) viremia after AHSCT. METHODS: Forty-nine patients who underwent AHSCT in our institution were prospectively enrolled...
May 22, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28507025/cutting-edge-defective-aerobic-glycolysis-defines-the-distinct-effector-function-in-antigen-activated-cd8-recent-thymic-emigrants
#7
Cody A Cunningham, Tessa Bergsbaken, Pamela J Fink
Recent thymic emigrants (RTEs) are the youngest peripheral T cells that have completed thymic selection and egress to the lymphoid periphery. RTEs are functionally distinct from their more mature but still naive T cell counterparts, because they exhibit dampened proliferation and reduced cytokine production upon activation. In this article, we show that, compared with more mature but still naive T cells, RTEs are impaired in their ability to perform aerobic glycolysis following activation. Impaired metabolism underlies the reduced IFN-γ production observed in activated RTEs...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28361127/longterm-maintenance-of-human-naive-t-cells-through-in-situ-homeostasis-in-lymphoid-tissue-sites
#8
Joseph J C Thome, Boris Grinshpun, Brahma V Kumar, Masa Kubota, Yoshiaki Ohmura, Harvey Lerner, Gregory D Sempowski, Yufeng Shen, Donna L Farber
Naïve T cells develop in the thymus and coordinate immune responses to new antigens; however, mechanisms for their long-term persistence over the human lifespan remain undefined. Here, we investigated human naïve T cell development and maintenance in primary and secondary lymphoid tissues obtained from individual organ donors aged 3 months-73 years. In the thymus, the frequency of double-positive thymocytes declined sharply in donors over age 40 coincident with reduced recent thymic emigrants (RTE) in lymphoid tissues, while naïve T cells were functionally maintained predominantly in lymph nodes (LN)...
December 2016: Science Immunology
https://www.readbyqxmd.com/read/28293817/cd4-memory-t-cells-retain-surface-expression-of-cd31-independently-of-thymic-function-in-patients-with-lymphoproliferative-disorders-following-autologous-hematopoietic-stem-cell-transplantation
#9
Egor V Batorov, Marina A Tikhonova, Irina V Kryuchkova, Vera V Sergeevicheva, Svetlana A Sizikova, Galina Y Ushakova, Dariya S Batorova, Andrey V Gilevich, Alexander A Ostanin, Ekaterina Y Shevela, Elena R Chernykh
High-dose chemotherapy with autologous hematopoietic stem-cell transplantation (AHSCT) causes severe and long-lasting immunodeficiency in patients with lymphoproliferative disorders. The thymus begins to restore the T-cell repertoire approximately from the sixth month post-transplant. We assessed the dynamics of post-transplant recovery of CD4(+)CD45RA(+)CD31(+) T cells, "recent thymic emigrants" (RTEs), and a poorly described subtype of CD4(+)CD45RA(-)CD31(+) T cells in 90 patients with lymphoproliferative disorders following high-dose chemotherapy with AHSCT...
July 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28284971/analysis-of-clinical-and-immunologic-phenotype-in-a-large-cohort-of-children-and-adults-with-cartilage-hair-hypoplasia
#10
Svetlana Kostjukovits, Paula Klemetti, Helena Valta, Timi Martelius, Luigi D Notarangelo, Mikko Seppänen, Mervi Taskinen, Outi Mäkitie
No abstract text is available yet for this article.
March 9, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28281185/sex-and-age-as-determinants-of-rat-t-cell-phenotypic-characteristics-influence-of-peripubertal-gonadectomy
#11
Nevena Arsenović-Ranin, Duško Kosec, Ivan Pilipović, Mirjana Nacka-Aleksić, Biljana Bufan, Zorica Stojić-Vukanić, Gordana Leposavić
The study examined the influence of age, sex and peripubertal gonadectomy on a set of T-cell phenotypic parameters. Rats of both sexes were gonadectomised at the age of 1 month and peripheral blood and spleen T lymphocytes from non-gonadectomised and gonadectomised 3- and 11-month-old rats were examined for the expression of differentiation/activation (CD90/CD45RC) and immunoregulatory markers. Peripheral blood T lymphocytes from non-gonadectomised rats showed age-dependent sexual dimorphisms in (1) total count (lower in female than male 11-month-old rats); (2) CD4+:CD8 + cell ratio (higher in female than male rats of both ages); (3) the proportion of recent thymic emigrants in CD8 + T cells (lower in female than male 3-month-old rats) and (4) the proportions of mature naïve and memory/activated cells (irrespective of age, the proportion of naïve cells was higher, whereas that of memory/activated cells was lower in females)...
March 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28157835/bacillus-calmette-gu%C3%A3-rin-vaccination-thymic-size-and-thymic-output-in-healthy-newborns
#12
Nina Marie Birk, Thomas Nørrelykke Nissen, Vera Zingmark, Jesper Kjærgaard, Lisbeth Marianne Thøstesen, Poul-Erik Kofoed, Lone Graff Stensballe, Andreas Andersen, Susanne Dam Nielsen, Christine Stabell Benn, Ole Pryds, Dorthe Lisbeth Jeppesen
BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial nonspecific effects on infant health. We aimed to examine the effect of BCG at birth on thymic size and the associations between thymic output, circulating lymphocytes, risk of infection, and thymic size. METHODS: In infants randomized to BCG or no BCG, thymic index (TI), and thymic/weight index (TWI) were measured by ultrasound at birth and at the age of 3 mo. T cell subpopulations including CD4(+) T cells, CD8(+) T cells, and recent thymic emigrants (RTEs) were assessed by flow cytometry...
June 2017: Pediatric Research
https://www.readbyqxmd.com/read/28154568/il-7-induced-proliferation-of-human-naive-cd4-t-cells-relies-on-continued-thymic-activity
#13
Susana L Silva, Adriana S Albuquerque, Paula Matoso, Bénédicte Charmeteau-de-Muylder, Rémi Cheynier, Dário Ligeiro, Miguel Abecasis, Rui Anjos, João T Barata, Rui M M Victorino, Ana E Sousa
Naive CD4 T-cell maintenance is critical for immune competence. We investigated here the fine-tuning of homeostatic mechanisms of the naive compartment to counteract the loss of de novo CD4 T-cell generation. Adults thymectomized in early childhood during corrective cardiac surgery were grouped based on presence or absence of thymopoiesis and compared with age-matched controls. We found that the preservation of the CD31(-) subset was independent of the thymus and that its size is tightly controlled by peripheral mechanisms, including prolonged cell survival as attested by Bcl-2 levels...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28142201/lymph-node-and-circulating-t-cell-characteristics-are-strongly-correlated-in-end-stage-renal-disease-patients-but-highly-differentiated-t-cells-reside-within-the-circulation
#14
B Dedeoglu, A E de Weerd, L Huang, A W Langerak, F J Dor, M Klepper, W Verschoor, D Reijerkerk, C C Baan, N H R Litjens, M G H Betjes
Ageing is associated with changes in the peripheral T cell immune system, which can be influenced significantly by latent cytomegalovirus (CMV) infection. To what extent changes in circulating T cell populations correlate with T cell composition of the lymph node (LN) is unclear, but is crucial for a comprehensive understanding of the T cell system. T cells from peripheral blood (PB) and LN of end-stage renal disease patients were analysed for frequency of recent thymic emigrants using CD31 expression and T cell receptor excision circle content, relative telomere length and expression of differentiation markers...
May 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28009290/inhibition-of-ror%C3%AE-t-skews-tcr%C3%AE-gene-rearrangement-and-limits-t-cell-repertoire-diversity
#15
Yanxia Guo, Kenzie D MacIsaac, Yi Chen, Richard J Miller, Renu Jain, Barbara Joyce-Shaikh, Heidi Ferguson, I-Ming Wang, Razvan Cristescu, John Mudgett, Laura Engstrom, Kyle J Piers, Gretchen A Baltus, Kenneth Barr, Hongjun Zhang, Huseyin Mehmet, Laxminarayan G Hegde, Xiao Hu, Laura L Carter, Thomas D Aicher, Gary Glick, Dennis Zaller, Abbas Hawwari, Craig C Correll, Dallas C Jones, Daniel J Cua
Recent studies have elucidated the molecular mechanism of RORγT transcriptional regulation of Th17 differentiation and function. RORγT was initially identified as a transcription factor required for thymopoiesis by maintaining survival of CD4(+)CD8(+) (DP) thymocytes. While RORγ antagonists are currently being developed to treat autoimmunity, it remains unclear how RORγT inhibition may impact thymocyte development. In this study, we show that in addition to regulating DP thymocytes survival, RORγT also controls genes that regulate thymocyte migration, proliferation, and T cell receptor (TCR)α selection...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/27942839/immune-modulation-associated-with-vascular-endothelial-growth-factor-vegf-blockade-in-patients-with-glioblastoma
#16
Alissa A Thomas, Jan L Fisher, Thomas H Hampton, Brock C Christensen, Gregory J Tsongalis, Gilbert J Rahme, Chery A Whipple, Sandra E Steel, Melissa C Davis, Arti B Gaur, Lionel D Lewis, Marc S Ernstoff, Camilo E Fadul
BACKGROUND: Vascular endothelial growth factor (VEGF), in addition to being pro-angiogenic, is an immunomodulatory cytokine systemically and in the tumor microenvironment. We previously reported the immunomodulatory effects of radiation and temozolomide (TMZ) in newly diagnosed glioblastoma. This study aimed to assess changes in peripheral blood mononuclear cell (PBMC) populations, plasma cytokines, and growth factor concentrations following treatment with radiation, TMZ, and bevacizumab (BEV)...
March 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27864993/thyrotropin-alters-t-cell-development-in-the-thymus-in-subclinical-hypothyroidism-mouse-model
#17
K Wu, M Zhao, C Ma, H Zhang, X Liu, L Zhou, J Zhao, L Gao, D Wang
Subclinical hypothyroidism (SCH) is highly prevalent in the general population and is associated with potential deleterious effects. Although developing T cells express thyroid-stimulating hormone receptor (TSH-R), the changes of T cell development in thymus in SCH have not been fully clarified. SCH mouse model, which is characterized by elevated serum TSH but similar thyroid hormone levels, was used to study the role of TSH in T cell development. Thymus weight of SCH mice increased 18% compared with controls...
January 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27769179/immune-recovery-in-acute-and-chronic-hiv-infection-and-the-impact-of-thymic-stromal-lymphopoietin
#18
Marco Gelpi, Hans J Hartling, Kristina Thorsteinsson, Jan Gerstoft, Henrik Ullum, Susanne D Nielsen
BACKGROUND: Symptomatic primary HIV infection is associated with an adverse prognosis, and immediate initiation of combination antiretroviral therapy (cART) is recommended. However, little is known about immunological predictors of immune recovery. Thymic Stromal Lymphopoietin (TSLP) is a cytokine that promotes CD4+ T cells homeostatic polyclonal proliferation and regulates Th17/regulatory T-cell balance, immunological functions known to be affected during primary HIV infection. The aim of this study was to describe immune recovery in primary and chronic HIV infection and possible impact of TSLP...
October 21, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27699228/decreases-in-thymopoiesis-of-astronauts-returning-from-space-flight
#19
Cara L Benjamin, Raymond P Stowe, Lisa St John, Clarence F Sams, Satish K Mehta, Brian E Crucian, Duane L Pierson, Krishna V Komanduri
Following the advent of molecular assays that measure T cell receptor excision circles (TRECs) present in recent thymic emigrants, it has been conclusively shown that thymopoiesis persists in most adults, but that functional output decreases with age, influencing the maintenance of a diverse and functional T cell receptor (TCR) repertoire. Space flight has been shown to result in a variety of phenotypic and functional changes in human T cells and in the reactivation of latent viruses. While space flight has been shown to influence thymic architecture in rodents, thymopoiesis has not previously been assessed in astronauts...
August 4, 2016: JCI Insight
https://www.readbyqxmd.com/read/27650411/aberrant-icos-t-cell-differentiation-in-women-with-spontaneous-preterm-labor
#20
Florian Kälble, Charlotte Mai, Miriam Wagner, Linda Schober, Matthias Schaier, Martin Zeier, Julia Spratte, Herbert Fluhr, Andrea Steinborn
PROBLEM: Recent studies revealed appropriate differentiation of recent thymic emigrant (RTE)-regulatory T cells (Tregs) to be crucial for maintaining healthy pregnancy. Currently, the role of responder T cells (Tresps) is not known. METHOD OF STUDY: Six-color flow cytometric analysis was used to detect differences in the differentiation of highly proliferative inducible co-stimulatory (ICOS)(+) -RTE-Tregs/Tresps and apoptosis-sensitive ICOS(-) -RTE-Tregs/Tresps into mature naïve (MN)-, CD31(+) -memory and CD31(-) -memory Tregs/Tresps in women with spontaneous preterm labor (sPL) compared to healthy pregnancy...
November 2016: American Journal of Reproductive Immunology: AJRI
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