Abstract
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.
Highlights
The immune system reconstitution in HIV-1- infected patients undergoing combined antiretroviral therapy is routinely evaluated by T-cell phenotyping, even though the infection impairs the B-cell mediated immunity
Here, the effect of Combined antiretroviral therapy (cART) on the mobilization of new B and T cells during a long follow-up (72 months) was analyzed by a duplex real-time PCR that combines the measure of T-cell receptor excision circles (TRECs) with the quantification of the “K deleting recombination excision circles” (KRECs) that assesses the extent of the B-cell output [23,24]
Quantification of KRECs and TRECs The number of KRECs and TRECs of HIV-1-infected patients was compared to that of matched HIV-1 uninfected controls
Summary
The immune system reconstitution in HIV-1- infected patients undergoing combined antiretroviral therapy is routinely evaluated by T-cell phenotyping, even though the infection impairs the B-cell mediated immunity. While TREC number in HIV-1infected patients has been found to correlate with different clinical-pathological parameters (age, plasma HIV-1 RNA, CD4+ T-lymphocyte counts, CD4+ T-lymphocyte percentages, and naive CD4+ T-lymphocyte number) and TREC number of HIV-1-infected children increases during cART [19,20,21,22], to our knowledge, no studies have investigated the effects of cART treatment on the release of new B lymphocytes from the bone marrow of treated patients. It is not known whether the recovery of B and T cells occurs simultaneously. Real-time PCR was used to quantify the mRNA expression of interleukin 7 (IL-7) and of the alpha chain of IL-7 receptor (IL-7Rα), while flow cytometry was used to evaluate the cell surface expression of IL-7Rα on CD4+ cells and the modulation of B- and T-cell subsets
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