Changes in Thymic Function With Age and During the Treatment of HIV Infection

Nature. 1998 Dec 17;396(6712):690-5. doi: 10.1038/25374.

Abstract

The thymus represents the major site of the production and generation of T cells expressing alphabeta-type T-cell antigen receptors. Age-related involution may affect the ability of the thymus to reconstitute T cells expressing CD4 cell-surface antigens that are lost during HIV infection; this effect has been seen after chemotherapy and bone-marrow transplantation. Adult HIV-infected patients treated with highly active antiretroviral therapy (HAART) show a progressive increase in their number of naive CD4-positive T cells. These cells could arise through expansion of existing naive T cells in the periphery or through thymic production of new naive T cells. Here we quantify thymic output by measuring the excisional DNA products of TCR-gene rearrangement. We find that, although thymic function declines with age, substantial output is maintained into late adulthood. HIV infection leads to a decrease in thymic function that can be measured in the peripheral blood and lymphoid tissues. In adults treated with HAART, there is a rapid and sustained increase in thymic output in most subjects. These results indicate that the adult thymus can contribute to immune reconstitution following HAART.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aging / immunology
  • Aging / physiology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cohort Studies
  • Gene Rearrangement, T-Lymphocyte
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • Humans
  • Infant
  • Infant, Newborn
  • Leukopoiesis
  • Middle Aged
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / drug effects
  • Thymus Gland / physiology*

Substances

  • Receptors, Antigen, T-Cell