Changes in thymic function with age and during the treatment of HIV infection
Department of Pediatrics; Program in Molecular Medicine
Medical Subject Headings
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.
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Citation: 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.