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 J. Picker and Richard A. Koup ()
Additional contact information
Daniel C. Douek: The University of Texas Southwestern Medical Center
Richard D. McFarland: The University of Texas Southwestern Medical Center
Philip H. Keiser: The University of Texas Southwestern Medical Center
Earl A. Gage: The University of Texas Southwestern Medical Center
Janice M. Massey: Duke University Medical Center
Barton F. Haynes: Duke University Medical Center
Michael A. Polis: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Ashley T. Haase: University of Minnesota Medical School
Mark B. Feinberg: Emory University School of Medicine
John L. Sullivan#: The University of Massachusetts Medical Center
Beth D. Jamieson: Division of Hematology-Oncology, Department of Medicine UCLA School of Medicine and UCLA Institute
Jerome A. Zack: Division of Hematology-Oncology, Department of Medicine UCLA School of Medicine and UCLA Institute
Louis J. Picker: The University of Texas Southwestern Medical Center
Richard A. Koup: The University of Texas Southwestern Medical Center

Nature, 1998, vol. 396, issue 6712, 690-695

Abstract: Abstract The thymus represents the major site of the production and generation of T cells expressing αβ-type T-cell antigen receptors1. Age-related involution2 may affect the ability of the thymus to reconstitute T cells expressing CD4 cell-surface antigens that are lost during HIV infection3; this effect has been seen after chemotherapy and bone-marrow transplantation4,5. Adult HIV-infected patients treated with highly active antiretroviral therapy (HAART) show a progressive increase in their number of naive CD4-positive T cells6,7. These cells could arise through expansion of existing naive T cells in the periphery8 or through thymic production of new naive T cells9,10. 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.

Date: 1998
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DOI: 10.1038/25374

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