Abstract

BackgroundWhile immunosenescence, defined as reduced production of new lymphocytes, restriction of T-cell receptor repertoire and telomeres shortening, has been extensively evaluated in HIV-infected children and adults, no data about these parameters are available in perinatally-infected patients with very long-lasting HIV infection.MethodsWe compared thymic and bone marrow output, telomere length (measured by Real-Time PCR) and T-cell receptor repertoire (determined by spectratyping) of 21 perinatally HIV-infected subjects (with a median of 27 years of infection) with those of 19 age-matched non-perinatally HIV-infected patients and 40 healthy controls. All patients received a combined antiretroviral therapy.ResultsWhile thymic and bone marrow output were not different among the analyzed groups, telomere length in peripheral blood cells and T-cell receptor diversity were significantly lower in HIV-perinatally and non-perinatally infected individuals compared to healthy controls.ConclusionsIn HIV-infected subjects, a normal thymic output together with a reduced telomere length and a restricted T-cell receptor repertoire could be explained by the shift of newly produced cells into memory subsets. This phenomenon may allow to control viral infection and maintain peripheral homeostasis.

Highlights

  • After the introduction of combined antiretroviral therapy, the rate of vertical HIV transmission drastically dropped to 1–2%, or even lower, in the United States and Western Europe [1]

  • Quantification of thymic and bone marrow output The number of TR excision circles (TRECs) and K-deleting recombination excision circles (KRECs) was simultaneously quantified by duplex quantitative Real-Time PCR, using DNA obtained from peripheral blood mononuclear cells, as previously reported [41]

  • DNA was extracted using QIAamp DNA Blood Mini Kit (Qiagen GmbH, Hilden, Germany), as recommended [43], from peripheral blood mononuclear cells obtained by Ficoll separation; its integrity was guaranteed by visualization on agarose gels, as suggested [44], while its quantity and quality were assessed on Nanodrop 2000 spectrophotometer

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Summary

Introduction

After the introduction of combined antiretroviral therapy (cART), the rate of vertical HIV transmission drastically dropped to 1–2%, or even lower, in the United States and Western Europe [1]. Peripheral T, B and NK lymphocytes of HIV-infected children and adults show features that have been considered as hallmarks of premature aging process Immunosenescence includes both a reduced production of new T and B cells and an increased proliferation of the existing T cells, leading to a restriction of T-cell receptor (TR) repertoire and to a more rapid telomere length (TL) shortening [7, 8]. While immunosenescence, defined as reduced production of new lymphocytes, restriction of T-cell receptor repertoire and telomeres shortening, has been extensively evaluated in HIV-infected children and adults, no data about these parameters are available in perinatally-infected patients with very long-lasting HIV infection

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