Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
Increases in T cell telomere length in HIV infection after antiretroviral combination therapy for HIV-1 infection implicate distinct population dynamics in CD4+ and CD8+ T cells [see comments]
Clin Immunol. 1999 Jul;92(1):14-24. Unique Identifier : AIDSLINE MED/99343947 Kaushal S; Landay AL; Lederman MM; Connick E; Spritzler J; Kuritzkes DR; Kessler H; Levine BL; St. Louis DC; June CH; Henry M. Jackson Foundation for the Advancement of Military; Medicine, U.S. Military HIV Research Program, Bethesda, Maryland; 20889, USA.
Abstract:
Changes in mean telomeric terminal restriction fragment (TRF) length were examined as a marker for cellular replicative history in HIV-1-infected individuals after institution of anti-retroviral therapy (ART). Increases in mean T cell TRF lengths were observed in most patients following therapy; however, the contribution of individual T cell subsets was complex. An elongation of CD8+ T cell TRF was nearly uniformly observed while changes in mean TRF length in CD4+ T cells were heterogeneous as, despite potent suppression of viral replication, CD4 cell telomeres recovered in some patients, yet continued to decline in others. Increases in CD8 cell TRF correlated with decreased memory cells, suggesting a negative selection in the periphery for CD8 cells with extensive replicative history. In contrast, increases in CD4+ T cell TRF length correlated with increases in naive cell subsets, suggesting that the CD4+ T cell TRF increase may reflect a thymic contribution in some patients. These are the first increases in somatic cell telomere length in a population of cells observed in vivo, and the findings are compatible with therapy-induced reconstitution of the lymphoid compartment with cells having a more extensive replicative potential. These findings further distinguish lymphocytes from other somatic cell populations where only decreases in TRF over time have been noted. Thus, institution of ART in persons with moderately advanced HIV-1 disease reveals distinct population dynamics of CD4 and CD8 T cell subsets and also shows that the lymphocyte replicative history is dynamic. Copyright 1999 Academic Press.
Keywords: JOURNAL ARTICLE Adult Anti-HIV Agents/*THERAPEUTIC USE Cell Division Cohort Studies CD4-Positive T-Lymphocytes/*VIROLOGY CD8-Positive T-Lymphocytes/*VIROLOGY Human HIV Infections/*DRUG THERAPY Immunophenotyping Lymphocyte Count/DRUG EFFECTS Middle Age Restriction Mapping Retroviridae/DRUG EFFECTS Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. T-Lymphocytes/CYTOLOGY Telomere/*GENETICS Comment in: Clin Immunol 1999 Jul;92(1):1-2
991030
A99A0906
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Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
