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

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

D C Douek  1 , R D McFarland, P H Keiser, E A Gage, J M Massey, B F Haynes, M A Polis, A T Haase, M B Feinberg, J L Sullivan, B D Jamieson, J A Zack, L J Picker, R A Koup
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Changes in thymic function with age and during the treatment of HIV infection

D C Douek et al. Nature. .

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.

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