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

The thymus represents the major site of the production and generation of T cells expressing alpha beta-type T-cell antigen receptors(1). Age-related i nvolution(2) may affect the ability of the thymus to reconstitute T cells e xpressing CD4 cell-surface antigens that are lost during HIV infection(3); this effect has been seen after chemotherapy and bone-marrow transplantatio n(4,5). Adult HIV-infected patients treated with highly active antiretrovir al therapy (HAART) show a progressive increase in their number of naive CD4 -positive T cells(6,7). These cells could arise through expansion of existi ng naive T cells in the periphery(8) or through thymic production of new na ive T cells(9,10). Here we quantify thymic output by measuring the excision al DNA products of TCR-gene rearrangement. We find that, although thymic fu nction declines with age, substantial output is maintained into late adulth ood. HIV infection leads to a decrease in thymic function that can be measu red in the peripheral blood and lymphoid tissues. In adults treated with HA ART, there is a rapid and sustained increase in thymic output in most subje cts. These results indicate that the adult thymus fan contribute to immune reconstitution following HAART.