Increased CD4+ T-lymphocyte senescence fraction in advanced human immunodeficiency virus type 1 infection.
Human immunodeficiency virus type 1 (HIV-1) infection is accompanied by peripheral CD4+ T-cell losses. CD4+ T-cell numbers often increase during antiviral treatment of acquired immune deficiency syndrome (AIDS), however, alterations in the CD4+ T-cell repertoire have not been completely corrected for these patients. Such individuals remain at increased risk of infection. Although senescence of the CD4+ T cells has not been adequately evaluated for advanced HIV-1 infection, hypothetically, replicative senescence could complicate therapeutic reconstitution of the CD4+ T cells in AIDS. In this study, correlates of replicative senescence, terminal restriction fragment (TRF) length and percentage short (< 5.0 kb) telomeric DNA (senescence fraction), were measured for the CD4+ T cells of HIV-1-infected patients with peripheral CD4+ T-cell counts of < 200/mm3. The results show that for advanced HIV-1 infection the TRF length of the CD4+ T cells is decreased (P < 0.01), and the senescence fraction increased (P < 0.05), when compared with uninfected controls. These findings suggest that cellular senescence may contribute to disruption of CD4+ T-cell diversity observed following the therapeutic, immunologic reconstitution of AIDS.
Nichols
W S
WS
Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, California 90048, USA.
Schneider
S
S
Chan
R C
RC
Farthing
C F
CF
Daar
E S
ES
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D016022:Case-Control Studies; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D015497:HIV-1; D006801:Humans; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics
D004247:DNA; D019098:Telomerase