Changes in thymic function with age and during the treatment of HIV infection

Daniel C. Douek, Richard D. McFarland, Philip H. Keiser, Earl A. Gage, Janice M. Massey, Barton F. Haynes, Michael A. Polis, Ashley T. Haase, Mark B. Feinberg, John L. Sullivan, Beth D. Jamieson, Jerome A. Zack, Louis Picker, Richard A. Koup

Research output: Contribution to journalArticle

1464 Scopus citations

Abstract

The thymus represents the major site of the production and generation of T cells expressing αβ-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.

Original languageEnglish (US)
Pages (from-to)690-695
Number of pages6
JournalNature
Volume396
Issue number6712
DOIs
Publication statusPublished - Dec 17 1998
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this

Douek, D. C., McFarland, R. D., Keiser, P. H., Gage, E. A., Massey, J. M., Haynes, B. F., ... Koup, R. A. (1998). Changes in thymic function with age and during the treatment of HIV infection. Nature, 396(6712), 690-695. https://doi.org/10.1038/25374