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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CD25 expressing CD8+ T cells are potent memory cells in old age.
Dietmar Herndler-Brandstetter,Susanne Schwaiger,Ellen Veel,Christine Fehrer,Daniel Cioca,Giovanni Almanzar,Michael Keller,Gerald Pfister,Walther Parson,Reinhard Würzner,Diether Schönitzer,Sian M. Henson,Richard Aspinall,Günter Lepperdinger,Beatrix Grubeck-Loebenstein +14 more
TL;DR: It is demonstrated that CD8+CD25+ memory T cells frequently exhibit a CD4+CD8+ double-positive phenotype and the expression of the CD8 αβ molecule and the occurrence of signal-joint TCR rearrangement excision circles suggest a thymic origin of these cells.
Journal ArticleDOI
Is immunosenescence influenced by our lifetime “dose” of exercise?
TL;DR: Recent theories for how exercise might influence T cell immunosenescence are discussed, exploring themes in the context of hotly debated issues in immunology.
Journal ArticleDOI
Immune reconstitution following hematopoietic stem-cell transplantation.
TL;DR: Therapies to improve immune function include vaccinations, immunoglobulins for recurrent infections, cytokines, and antigen-specific donor lymphocyte infusions.
Journal ArticleDOI
Programmed Death-1 Is a Marker for Abnormal Distribution of Naive/Memory T Cell Subsets in HIV-1 Infection
Gaëlle Breton,Nicolas Chomont,Hiroshi Takata,Rémi Fromentin,Jeffrey D. Ahlers,Abdelali Filali-Mouhim,Catherine Riou,Mohamed Rachid Boulassel,Jean-Pierre Routy,Bader Yassine-Diab,Rafick Pierre Sekaly +10 more
TL;DR: It is shown that PD-1 is upregulated on all T cell subsets, including naive, central memory, and transitional memory T cells in HIV-1–infected subjects, and is identified as a marker for aberrant distribution of Tcell subsets inAIDS.
Journal ArticleDOI
Host T Cells Resist Graft-Versus-Host Disease Mediated by Donor Leukocyte Infusions
Bruce R. Blazar,Christopher J. Lees,Paul J. Martin,Randolph J. Noelle,Byoung S. Kwon,William J. Murphy,Patricia A. Taylor +6 more
TL;DR: Host T cells, which are capable of generating antidonor CTL effector cells, are responsible for the impaired ability ofDLI to induce GVHD, and these same mechanisms may limit the efficacy of DLI in cancer therapy under some conditions.
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.