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

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.