Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging

J Immunol. 2008 Jul 15;181(2):1573-81. doi: 10.4049/jimmunol.181.2.1573.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Child
  • Child, Preschool
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1
  • Humans
  • Infant
  • Ki-67 Antigen / immunology
  • Ki-67 Antigen / metabolism*
  • Lymphocyte Activation
  • Middle Aged
  • Platelet Endothelial Cell Adhesion Molecule-1 / immunology
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism*
  • T-Lymphocyte Subsets / immunology

Substances

  • Ki-67 Antigen
  • Platelet Endothelial Cell Adhesion Molecule-1