Effects of combined antiretroviral therapy on B- and T-cell release from production sites in long-term treated HIV-1+ patients

Journal of Translational Medicine

Research

Carlo Torti¹  Eugenia Quiros-Roldan¹  Daria Gotti¹  Marco Chiarini²  Cinzia Zanotti²  Luigi Caimi²  Alessandra Sottini²  Federico Serana²  Luisa Imberti² 

[1] Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy;Laboratory of Biotechnology, Diagnostics Department, Spedali Civili of Brescia, Brescia, Italy;

关键词: KRECs;    TRECs;    HIV-1;    cART;    T lymphocytes;    B lymphocytes;   

DOI  :  10.1186/1479-5876-10-94

 received in 2012-01-19, accepted in 2012-04-24,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe immune system reconstitution in HIV-1- infected patients undergoing combined antiretroviral therapy is routinely evaluated by T-cell phenotyping, even though the infection also impairs the B-cell mediated immunity. To find new laboratory markers of therapy effectiveness, both B- and T- immune recovery were evaluated by means of a follow-up study of long-term treated HIV-1- infected patients, with a special focus on the measure of new B- and T-lymphocyte production.MethodsA longitudinal analysis was performed in samples obtained from HIV-1-infected patients before therapy beginning and after 6, 12, and 72 months with a duplex real-time PCR allowing the detection of K-deleting recombination excision circles (KRECs) and T-cell receptor excision circles (TRECs), as measures of bone-marrow and thymic output, respectively. A cross sectional analysis was performed to detect B- and T-cell subsets by flow cytometry in samples obtained at the end of the follow-up, which were compared to those of untreated HIV-1-infected patients and uninfected controls.ResultsThe kinetics and the timings of B- and T-cell release from the bone marrow and thymus during antiretroviral therapy were substantially different, with a decreased B-cell release and an increased thymic output after the prolonged therapy. The multivariable regression analysis showed that a longer pre-therapy infection duration predicts a minor TREC increase and a major KREC reduction.ConclusionsThe quantification of KRECs and TRECs represents an improved method to monitor the effects of therapies capable of influencing the immune cell pool composition in HIV-1-infected patients.

【 授权许可】

Unknown   
© Quiros-Roldan et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.