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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Investigation of recombinant human insulin-like growth factor type I in thymus regeneration in the acute stage of experimental FIV infection in juvenile cats.
TL;DR: Thymus involvement and the development of thymic lesions in HIV-1 infection is hypothesized to suppress thymus function and limit T cell maturation and replenishment of the peripheral lymphoid pool, and thymotrophic agents, such as insulin-like growth factor type I (IGF-I), may represent adjunctive but important methods of treatment to protect or promote thymUS function.
Journal ArticleDOI
Specific patterns of CD4-associated immunosenescence in vertically HIV-infected subjects.
Gema Méndez-Lagares,Laura Cardona Diaz,Rafael Correa-Rocha,J.A. León Leal,Sara Ferrando-Martinez,Ezequiel Ruiz-Mateos,María del Mar del Pozo-Balado,María Dolores Gurbindo,M.I. de José,María Ángeles Muñoz-Fernández,Manuel Leal,Yolanda M. Pacheco +11 more
TL;DR: Despite long periods of infection, vertically HIV-infected subjects show specific patterns of immunosenescence, revealing a preserved CD4 T-cell homeostasis for subset differentiation and distribution.
Journal ArticleDOI
IL-7 and SCF Levels Inversely Correlate with T Cell Reconstitution and Clinical Outcomes after Cord Blood Transplantation in Adults.
Ioannis Politikos,Haesook T. Kim,Sarah Nikiforow,Lequn Li,Julia A. Brown,Joseph H. Antin,Corey Cutler,Karen K. Ballen,Jerome Ritz,Vassiliki A. Boussiotis +9 more
TL;DR: IL-7 and SCF are elevated for a prolonged period after dUCBT and persistently high levels of these cytokines may correlate with worse clinical outcomes.
Journal ArticleDOI
Generation and Regeneration of Thymic Epithelial Cells.
TL;DR: The current understanding of the development and function of thymic epithelial cells is summarized, and this to strategies to protect and/or restore thymi epithelial cell function for therapeutic benefit is related.
Journal ArticleDOI
T-cell Receptor and K-deleting Recombination Excision Circles in Newborn Screening of T- and B-cell Defects: Review of the Literature and Future Challenges.
Marco Chiarini,Cinzia Zanotti,Federico Serana,Alessandra Sottini,Diego Bertoli,Luigi Caimi,Luisa Imberti +6 more
TL;DR: Efforts are now being made to establish a screen for B-cell defects, in particular agammaglobulinaemia, taking advantage of the introduction of the method for the quantification of K-deleting recombination excision circles (KRECs).
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.