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 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.
Douek
D C
DC
Department of Medicine, The University of Texas Southwestern Medical Center, Dallas 75235, USA.
McFarland
R D
RD
Keiser
P H
PH
Gage
E A
EA
Massey
J M
JM
Haynes
B F
BF
Polis
M A
MA
Haase
A T
AT
Feinberg
M B
MB
Sullivan
J L
JL
Jamieson
B D
BD
Zack
J A
JA
Picker
L J
LJ
Koup
R A
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015329:Gene Rearrangement, T-Lymphocyte; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019891:Leukopoiesis; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D011948:Receptors, Antigen, T-Cell