De novo T-cell generation in patients at different ages and stages of HIV-1 disease.
We assessed de novo T-cell generation by determining T-cell receptor-rearrangement excision circles (TRECs) based on patient age and on stage of HIV-1 infection. TRECs were measured in purified CD4 and CD8 T cells of a large cohort of HIV-1-infected subjects (n = 297) with chronic infection but no previous antiretroviral treatment and of a control group of HIV-negative subjects (n = 120). HIV-1-infected subjects were stratified on the basis of CD4 T-cell counts in 3 groups, early-stage disease (more than 500 CD4 T cells), intermediate-stage disease (200-500 CD4 T cells), and late-stage disease (fewer than 200 CD4 T cells). Compared with the control group, CD8 TREC contents were severely reduced (P <.001) in HIV-1-infected subjects regardless of the stage of HIV disease. In contrast, CD4 TREC contents were significantly increased (P =.003) in HIV-1-infected subjects during early-stage disease, similar at intermediate-stage disease, and severely reduced only at late-stage disease. We show that the increase in CD4 TRECs was mostly limited to younger (younger than 45 years) patients at early-stage disease. Our results demonstrate a dichotomy between TREC contents in CD4 and CD8 T-cell populations in HIV-1 infection and indicate that thymus function in younger subjects is preserved at early and intermediate stages of HIV infection.
Nobile
Massimo
M
Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Rue Bugnon, 1011 Lausanne, Switzerland.
Correa
Rafael
R
Borghans
José A M
JA
D'Agostino
Claudia
C
Schneider
Philippe
P
De Boer
Rob J
RJ
Pantaleo
Giuseppe
G
D000328:Adult; D000375:Aging / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology; D016923:Cell Death / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D015329:Gene Rearrangement, T-Lymphocyte; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D008875:Middle Aged; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D019562:Viral Load