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Recent thymic emigrant

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 Philippe', 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, only few reports exist on milder primary antibody deficiencies like idiopathic primary hypogammaglobulinemia and IgG subclass deficiency. We performed flow cytometric immunophenotyping in 33 common variable immunodeficiency, 23 idiopathic primary hypogammaglobulinemia and 21 IgG subclass deficiency patients, and in 47 asymptomatic first-degree family members of patients and 101 unrelated healthy controls...
September 15, 2016: 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...
August 4, 2016: 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
J R Artalejo, A Gómez-Corral, M López-García, C Molina-París
The population of naive T cells in the periphery is best described by determining both its T cell receptor diversity, or number of clonotypes, and the sizes of its clonal subsets. In this paper, we make use of a previously introduced mathematical model of naive T cell homeostasis, to study the fate and potential of naive T cell clonotypes in the periphery. This is achieved by the introduction of several new stochastic descriptors for a given naive T cell clonotype, such as its maximum clonal size, the time to reach this maximum, the number of proliferation events required to reach this maximum, the rate of contraction of the clonotype during its way to extinction, as well as the time to a given number of proliferation events...
June 27, 2016: Journal of Mathematical Biology
Nelli Heikkilä, Sini M Laakso, Helga Mannerström, Eliisa Kekäläinen, Päivi Saavalainen, Hanna Jarva, Tommi P Arstila
PURPOSE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare human autoimmune disorder caused by mutations in the AIRE (autoimmune regulator) gene. Loss of AIRE disrupts thymic negative selection and gives rise to impaired cytotoxic and regulatory T cell populations. To date, CD4(+) T helper (Th) cells remain little studied. This study aims to elucidate their role in APECED pathogenesis. METHODS: Th cells were explored in ten APECED patients and ten healthy controls using cell culture assays, multiparameter flow cytometry, and transcriptome analysis...
August 2016: Journal of Clinical Immunology
K V Shmagel, E V Saidakova, N G Shmagel, L B Korolevskaya, V A Chereshnev, J Robinson, J-C Grivel, D C Douek, L Margolis, D D Anthony, M M Lederman
OBJECTIVES: Chronic hepatitis C virus (HCV) and HIV viral infections are characterized by systemic inflammation. Yet the relative levels, drivers and correlates of inflammation in these settings are not well defined. METHODS: Seventy-nine HIV-infected patients who had been receiving antiretroviral therapy (ART) for more than 2 years and who had suppressed plasma HIV levels (< 50 HIV-1 RNA copies/mL) were included in the study. Two patient groups, HCV-positive/HIV-positive and HCV-negative/HIV-positive, and a control group comprised of healthy volunteers (n = 20) were examined...
September 2016: HIV Medicine
Travis J Friesen, Qingyong Ji, Pamela J Fink
T cell development requires a period of postthymic maturation. Why this is the case has remained a mystery, particularly given the rigors of intrathymic developmental checkpoints, successfully traversed by only ∼5% of thymocytes. We now show that the first few weeks of T cell residence in the lymphoid periphery define a period of heightened susceptibility to tolerance induction to tissue-restricted antigens (TRAs), the outcome of which depends on the context in which recent thymic emigrants (RTEs) encounter antigen...
May 30, 2016: Journal of Experimental Medicine
Hye Kyung Kim, Adam T Waickman, Ehydel Castro, Francis A Flomerfelt, Nga V Hawk, Veena Kapoor, William G Telford, Ronald E Gress
IL-7 is essential for T-cell survival but its availability is limited in vivo. Consequently, all peripheral T cells, including recent thymic emigrants (RTEs) are constantly competing for IL-7 to survive. RTEs are required to replenish TCR diversity and rejuvenate the peripheral T-cell pool. However, it remains unknown how RTEs successfully compete with resident mature T cells for IL-7. Moreover, RTEs express low levels of IL-7 receptors, presumably rendering them even less competitive. Here, we show that, surprisingly, RTEs are more responsive to IL-7 than mature naïve T cells as demonstrated by markedly increased STAT5 phosphorylation upon IL-7 stimulation...
July 2016: European Journal of Immunology
Jamal Bamoulid, Cécile Courivaud, Thomas Crepin, Clémence Carron, Emilie Gaiffe, Caroline Roubiou, Caroline Laheurte, Bruno Moulin, Luc Frimat, Philippe Rieu, Christiane Mousson, Antoine Durrbach, Anne-Elisabeth Heng, Jean-Michel Rebibou, Philippe Saas, Didier Ducloux
Lack of clear identification of patients at high risk of acute rejection hampers the ability to individualize immunosuppressive therapy. Here we studied whether thymic function may predict acute rejection in antithymocyte globulin (ATG)-treated renal transplant recipients in 482 patients prospectively studied during the first year post-transplant of which 86 patients experienced acute rejection. Only CD45RA(+)CD31(+)CD4(+) T cell (recent thymic emigrant [RTE]) frequency (RTE%) was marginally associated with acute rejection in the whole population...
May 2016: Kidney International
Inna Menkova-Garnier, Hakim Hocini, Emile Foucat, Pascaline Tisserand, Laure Bourdery, Constance Delaugerre, Clarisse Benne, Yves Lévy, Jean-Daniel Lelièvre
Peripheral CD4+ T-cell levels are not fully restored in a significant proportion of HIV+ individuals displaying long-term viral suppression on c-ART. These immunological nonresponders (INRs) have a higher risk of developing AIDS and non-AIDS events and a lower life expectancy than the general population, but the underlying mechanisms are not fully understood. We used an in vitro system to analyze the T- and B-cell potential of CD34+ hematopoietic progenitor cells. Comparisons of INRs with matched HIV+ patients with high CD4+ T-cell counts (immune responders (IRs)) revealed an impairment of the generation of T-cell progenitors, but not of B-cell progenitors, in INRs...
April 2016: PLoS Pathogens
Aina Teniente-Serra, José Vicente Hervás, Bibiana Quirant-Sánchez, María José Mansilla, Laia Grau-López, Cristina Ramo-Tello, Eva María Martínez-Cáceres
AIMS: Fingolimod, oral treatment for relapsing-remitting multiple sclerosis (RRMS), is an agonist of sphingosine and its metabolite S1P that binds their receptors, blocking the egress of lymphocytes from lymph nodes. The aim of this study was immunomonitoring of minor peripheral lymphocyte subpopulations in RRMS patients under treatment with fingolimod and correlation with treatment response. METHODS: Prospective study. T- and B-cell subpopulations were analyzed using multiparametric flow cytometry in peripheral blood from 14 RRMS patients under treatment with fingolimod at baseline, +1, +3, +6, +9, and +12 months of follow-up...
July 2016: CNS Neuroscience & Therapeutics
Ketty Gianesin, Antoni Noguera-Julian, Marisa Zanchetta, Paola Del Bianco, Maria Raffaella Petrara, Riccardo Freguja, Osvalda Rampon, Clàudia Fortuny, Mireia Camós, Elena Mozzo, Carlo Giaquinto, Anita De Rossi
OBJECTIVE: Several pieces of evidence indicate that HIV-infected adults undergo premature aging. The effect of HIV and antiretroviral therapy (ART) exposure on the aging process of HIV-infected children may be more deleterious since their immune system coevolves from birth with HIV. DESIGN: Seventy-one HIV-infected (HIV+), 65 HIV-exposed-uninfected (HEU), and 56 HIV-unexposed-uninfected (HUU) children, all aged 0-5 years, were studied for biological aging and immune senescence...
June 1, 2016: AIDS
Ute Bank, Katrin Deiser, Daniela Finke, Günter J Hämmerling, Bernd Arnold, Thomas Schüler
In adult mice, lymphopenia-induced proliferation (LIP) leads to T cell activation, memory differentiation, tissue destruction, and a loss of TCR diversity. Neonatal mice are lymphopenic within the first week of life. This enables some recent thymic emigrants to undergo LIP and convert into long-lived memory T cells. Surprisingly, however, most neonatal T cells do not undergo LIP. We therefore asked whether neonate-specific mechanisms prevent lymphopenia-driven T cell activation. In this study, we show that IL-7R-dependent innate lymphoid cells (ILCs) block LIP of CD8(+) T cells in neonatal but not adult mice...
May 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
B Dedeoglu, R W J Meijers, M Klepper, D A Hesselink, C C Baan, N H R Litjens, M G H Betjes
Patients with end-stage renal disease have prematurely aged T cell systems. We tested whether T cell aging parameters were associated with the risk of infections after renal transplantation (RTx). We studied 188 patients over 1 year. Peripheral T cells were analyzed before and at 3 and 6 mo after RTx for frequency of recent thymic emigrants, relative telomere length and differentiation status. These parameters were related to the occurrence of opportunistic and serious infections. Overall, 84 patients developed an infection...
August 2016: American Journal of Transplantation
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