Journal ArticleDOI
Changes in thymic function with age and during the treatment of HIV infection
Daniel C. Douek,Richard D. McFarland,Phillip H. Keiser,Earl A. Gage,Janice M. Massey,Barton F. Haynes,Michael A. Polis,Ashley T. Haase,Mark B. Feinberg,John L. Sullivan,Beth D. Jamieson,Jerome A. Zack,Louis J. Picker,Richard A. Koup +13 more
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TLDR
It is found that, although thymic function declines with age, substantial output is maintained into late adulthood and this results indicate that the adult thymus can contribute to immune reconstitution following HAART.Abstract:
The thymus represents the major site of the production and generation of T cells expressing alphabeta-type T-cell antigen receptors. Age-related involution may affect the ability of the thymus to reconstitute T cells expressing CD4 cell-surface antigens that are lost during HIV infection; this effect has been seen after chemotherapy and bone-marrow transplantation. Adult HIV-infected patients treated with highly active antiretroviral therapy (HAART) show a progressive increase in their number of naive CD4-positive T cells. These cells could arise through expansion of existing naive T cells in the periphery or through thymic production of new naive T cells. Here we quantify thymic output by measuring the excisional DNA products of TCR-gene rearrangement. We find that, although thymic function declines with age, substantial output is maintained into late adulthood. HIV infection leads to a decrease in thymic function that can be measured in the peripheral blood and lymphoid tissues. In adults treated with HAART, there is a rapid and sustained increase in thymic output in most subjects. These results indicate that the adult thymus can contribute to immune reconstitution following HAART.read more
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Reversing T cell immunosenescence: why, who, and how.
TL;DR: This review provides evidences of the central role played by cell-mediated immunity in the immunosenescence process and explores the means by which senescent state of the cell- mediated immune function could be identified and predicted using biomarkers.
Journal ArticleDOI
Quantification of T cell receptor rearrangement excision circles to estimate thymic function: an important new tool for endocrine-immune physiology.
Vincent Geenen,J. F. Poulin,M. L. Dion,Henri Martens,Emilie Castermans,Isabelle Hansenne,Michel Moutschen,R. P. Sekaly,Rémi Cheynier +8 more
TL;DR: How TREC quantification is a powerful and reliable method to evaluate the impact of hormones and endocrine disorders upon thymic function is described.
Journal ArticleDOI
The different extent of B and T cell immune reconstitution after hematopoietic stem cell transplantation and enzyme replacement therapies in SCID patients with adenosine deaminase deficiency.
Federico Serana,Alessandra Sottini,Marco Chiarini,Cinzia Zanotti,Claudia Ghidini,Arnalda Lanfranchi,Lucia Dora Notarangelo,Luigi Caimi,Luisa Imberti +8 more
TL;DR: It is found that immune reconstitution was different following the two treatments of hematopoietic stem cell transplantation and enzyme replacement therapy with pegylated bovine ADA, and it was compromised in children receiving prolonged PEG-ADA therapy, whose T cells showed progressively narrowing T cell repertoires.
Journal ArticleDOI
CD4+CD25+FOXP3+ T regulatory cells reconstitute and accumulate in the bone marrow of patients with multiple myeloma following allogeneic stem cell transplantation.
Djordje Atanackovic,Yanran Cao,Tim Luetkens,Jens Panse,Christiane Faltz,Julia Arfsten,Katrin Bartels,Christine Wolschke,Thomas Eiermann,Axel R. Zander,Boris Fehse,Carsten Bokemeyer,Nicolaus Kröger +12 more
TL;DR: Allogeneic stem cell transplantation provides a short but significant window of opportunity for CD8+ T cells before an exuberant regeneration of immunosuppressive Treg sets in, and is suggested to undermine persistent immune control of multiple myeloma.
References
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Journal ArticleDOI
Positive Effects of Combined Antiretroviral Therapy on CD4+ T Cell Homeostasis and Function in Advanced HIV Disease
Brigitte Autran,Guislaine Carcelain,T.S. Li,Catherine Blanc,Dominique Mathez,R. Tubiana,C. Katlama,Patrice Debré,Jacques Leibowitch +8 more
TL;DR: In this article, a three-phase T cell reconstitution was demonstrated after HAART, with an early rise of memory CD4(+) cells, a reduction in T cell activation correlated to the decreasing retroviral activity together with an improved CD4+ T cell reactivity to recall antigens.
Journal ArticleDOI
High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR
Michael Piatak,Michael S. Saag,Limei C. Yang,Stephen J. Clark,John C. Kappes,K.-C. Luk,Beatrice H. Hahn,George M. Shaw,Jeffrey D. Lifson +8 more
TL;DR: Quantitation of HIV-1 in plasma by QC-PCR may be useful in assessing the efficacy of antiretroviral agents, especially in early stage disease when conventional viral markers are often negative.
Journal ArticleDOI
Immunopathogenesis of human immunodeficiency virus infection
TL;DR: In this paper, the role of LFA-1 has been highlighted, and several factors in addition to endogenous viral regulatory proteins have been reported as capable of modulating the state of viral latency and expression in vitro.
Journal ArticleDOI
Age, thymopoiesis, and CD4+ t-lymphocyte regeneration after intensive chemotherapy
Crystal L. Mackall,Thomas A. Fleisher,Margaret R. Brown,Mary P. Andrich,Clara C. Chen,Irwin M. Feuerstein,Marc E. Horowitz,Ian T. Magrath,Aziza T. Shad,Seth M. Steinberg,Leonard H. Wexler,Ronald E. Gress +11 more
TL;DR: Thymus-dependent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway, and the results suggest that rapid T-cell regeneration requires residual thymic function in patients receiving high-dose chemotherapy.
Journal ArticleDOI
Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation
Nadine Pakker,Daan W. Notermans,Rob J. de Boer,Marijke T. L. Roos,Frank de Wolf,Andrew M. Hill,John M. Leonard,Sven A. Danner,Frank Miedema,Peter Th. A. Schellekens +9 more
TL;DR: It is shown, using mathematical modeling, that redistribution of T cells to the blood can explain the striking correlation between the initial CD4+ and CD8+ memory T-cell repopulation and the observation that 3 weeks after the start of treatment memory CD4-cell numbers reach a plateau.