Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging
Vrisekoop, N.; van Gent, R.; de Boer, A.B.; Otto, S.A.; Borleffs, J.C.C.; Steingrover, R.; Prins, J.M.; Kuijpers, T.W.; Wolfs, T.F.W.; Geelen, S.P.M.; Vulto, I.; Lansdorp, P.; Tesselaar, N.A.; Borghans, J.A.M.; Miedema, F.
(2008) Journal of Immunology, volume 181, issue 2, pp. 1573 - 1581
(Article)
Abstract
It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery. In addition to measuring T cell activation and proliferation
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markers, CD4 T cell generation and aging of the CD4 T cell compartment were assessed by measuring TCR excision circles and the fraction of CD31-expressing naive CD4 T cells. In all children and in adults with relatively high CD4 T cell counts at start of therapy (>200 cells/μl), total CD4 T cell numbers normalized within 1 year of therapy. After long-term HAART (4.4–9.6 years), naive CD4 T cell counts had normalized in both groups. Although in adults with low baseline CD4 T cell counts (<200 cells/μl) total CD4 T cell numbers normalized eventually after at least 7 years of HAART, naive CD4 T cell counts had still not recovered. TCR excision circle data showed that thymic T cell production contributed to naive T cell recovery at all ages. The fraction of CD31-expressing naive CD4 T cells was found to be normal, suggesting that the CD4 T cell repertoire was diverse after long-term HAART. Hence, under sustained viral suppression during long-term HAART, the T cell compartment has the potential to fully recover by generating new naive T cells both in children and in adults with high baseline CD4 T cells counts. Irrespective of baseline CD4 T cell counts, reconstitution occurred without a significant effect on T cell aging as reflected by markers for replicative history.
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Keywords: Adolescent, Adult, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes/drug effects, Child, Child, Preschool, HIV Infections/drug therapy, HIV-1, Humans, Infant, Ki-67 Antigen/immunology, Lymphocyte Activation, Middle Aged, Platelet Endothelial Cell Adhesion Molecule-1/immunology, T-Lymphocyte Subsets/immunology, 1 - Taverne, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 0022-1767
Publisher: American Association of Immunologists
(Peer reviewed)