title: Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging.
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 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/microl), 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/microl) 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.
authors.affiliation: Department of Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Nienke
authors.initials: N
authors.lastname: Vrisekoop
authors.forename: Rogier
authors.initials: R
authors.lastname: van Gent
authors.forename: Anne Bregje
authors.initials: AB
authors.lastname: de Boer
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Otto
authors.forename: Jan C C
authors.initials: JC
authors.lastname: Borleffs
authors.forename: Radjin
authors.initials: R
authors.lastname: Steingrover
authors.forename: Jan M
authors.initials: JM
authors.lastname: Prins
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.forename: Tom F W
authors.initials: TF
authors.lastname: Wolfs
authors.forename: Sibyl P M
authors.initials: SP
authors.lastname: Geelen
authors.forename: Irma
authors.initials: I
authors.lastname: Vulto
authors.forename: Peter
authors.initials: P
authors.lastname: Lansdorp
authors.forename: Kiki
authors.initials: K
authors.lastname: Tesselaar
authors.forename: José A M
authors.initials: JA
authors.lastname: Borghans
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007223:Infant; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1