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Recent thymic emigrants

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...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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
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...
March 14, 2017: International Journal of Hematology
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
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
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 months. T cell subpopulations including CD4(+) T cells, CD8(+) T cells, and recent thymic emigrants (RTEs) were assessed by flow cytometry...
February 3, 2017: Pediatric Research
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
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
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
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
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
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
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
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
Delfien J A Bogaert, Marieke De Bruyne, Veronique Debacker, Pauline Depuydt, Katleen De Preter, Carolien Bonroy, Jan Philippé, Victoria Bordon, Bart N Lambrecht, Tessa Kerre, Andrea Cerutti, Karim Y Vermaelen, Filomeen Haerynck, Melissa Dullaers
The etiology of primary antibody deficiencies is largely unknown. Beside rare monogenic forms, the majority of cases seem to have a more complex genetic basis. Whereas common variable immunodeficiency has been investigated in depth, there are only a few reports on milder primary antibody deficiencies such as idiopathic primary hypogammaglobulinemia and IgG subclass deficiency. We performed flow cytometric immunophenotyping in 33 patients with common variable immunodeficiency, 23 with idiopathic primary hypogammaglobulinemia and 21 with IgG subclass deficiency, as well as in 47 asymptomatic first-degree family members of patients and 101 unrelated healthy controls...
January 2017: Haematologica
Štefan Blazina, Alojz Ihan, Luca Lovrečić, Tinka Hovnik
Antibody deficiency is common finding in patients with Jacobsen syndrome (JS). In addition, there have been few reports of T-cell defects in this condition, possibly because most of the reported patients have not been specifically evaluated for T-cell function. In this article, we present a child with an 11q deletion and combined immunodeficiency and we perform a literature overview on immunodeficiency in JS. Our patient presented with recurrent bacterial and prolonged viral infections involving the respiratory system, as well as other classic features of the syndrome...
September 8, 2016: American Journal of Medical Genetics. Part A
Jonah S Zitsman, Paula Alonso-Guallart, Christopher Ovanez, Yojiro Kato, Joanna F Rosen, Joshua I Weiner, Raimon Duran-Struuck
Cynomolgus macaques (CYNO; Macaca fascicularis) are a well-established NHP model used for studies in immunology. To provide reference values on the baseline cell distributions in the hematopoietic and lymphoid organs (HLO) of these animals, we used flow cytometry to analyze the peripheral blood, bone marrow, mesenteric lymph nodes, spleen, and thymus of a cohort of male, adult, research-naïve, Mauritian CYNO. Our findings demonstrate that several cell distribution patterns differ between CYNO and humans. First, the CD4(+):CD8(+) T-cell ratio is lower in CYNO compared with humans...
2016: Comparative Medicine
Y Oulhote, Z Shamim, K Kielsen, P Weihe, P Grandjean, L P Ryder, C Heilmann
BACKGROUND: To explore possible markers of developmental immunotoxicity, we prospectively examined 56 children to determine associations between exposures to methylmercury and persistent organic pollutants since birth and the comprehensive differential counts of white blood cells (WBC) at age 5 years. MATERIALS AND METHODS: Extended differential count included: neutrophils, eosinophils, basophils, lymphocytes (includingT cells, NK cells, and B cells), and monocytes...
March 2017: Reproductive Toxicology
Dao-Ping Sun, Hui Jin, Chong-Yang Ding, Jin-Hua Liang, Li Wang, Lei Fan, Yu-Jie Wu, Wei Xu, Jian-Yong Li
To investigate the thymic regenerative potential in adults accepting chemotherapy for lymphoma. The dynamics of thymic activity in 54 adults from baseline to 12 mo post-chemotherapy was analyzed by assessing thymic structural changes with serial computed tomography (CT) scans, and correlating these with measurements of thymic output by concurrent analysis of single-joint (sj) T-cell receptor excision circles (sjTREC) and CD31(+) recent thymic emigrants (RTE) in peripheral blood. Furthermore, the consequence of thymic renewal on peripheral CD4(+) T cell recovery after chemotherapy was evaluated...
May 2016: Oncoimmunology
Josué Pérez-Santiago, Dan Ouchi, Victor Urrea, Jorge Carrillo, Cecilia Cabrera, Jordi Villà-Freixa, Jordi Puig, Roger Paredes, Eugènia Negredo, Bonaventura Clotet, Marta Massanella, Julià Blanco
BACKGROUND: The failure to increase CD4 T-cell counts in some antiretroviral therapy suppressed participants (immunodiscordance) has been related to perturbed CD4 T-cell homeostasis and impacts clinical evolution. METHODS: We evaluated different definitions of immunodiscordance based on CD4 T-cell counts (cutoff) or CD4 T-cell increases from nadir value (ΔCD4) using supervised random forest classification of 74 immunological and clinical variables from 196 antiretroviral therapy suppressed individuals...
September 24, 2016: AIDS
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