Changes in thymic function with age and during the treatment of HIV infection
Department of Pediatrics; Program in Molecular Medicine
Adolescent; Adult; Aged; Aging; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Gene Rearrangement, T-Lymphocyte; HIV Infections; Humans; Infant; Infant, Newborn; Leukopoiesis; Middle Aged; Polymerase Chain Reaction; Receptors, Antigen, T-Cell; Thymus Gland
Immunology and Infectious Disease | Pediatrics
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.
DOI of Published Version
Nature. 1998 Dec 17;396(6712):690-5. Link to article on publisher's site
Douek, Daniel C.; McFarland, Richard D.; Keiser, Phillip H.; Gage, Earl A.; Massey, Janice M.; Haynes, Barton F.; Polis, Michael A.; Haase, Ashley T.; Feinberg, Mark B.; Sullivan, John L.; Jamieson, Beth D.; Zack, Jerome A.; Picker, Louis J.; and Koup, Richard A., "Changes in thymic function with age and during the treatment of HIV infection" (1998). Immunology/Infectious Disease. 3.