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

DC Douek, RD McFarland, PH Keiser, EA Gage… - Nature, 1998 - nature.com
DC Douek, RD McFarland, PH Keiser, EA Gage, JM Massey, BF Haynes, MA Polis…
Nature, 1998nature.com
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 …
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.
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