Effect of didanosine, stavudine, and hydroxyurea therapy on apoptosis in CD45RA+ and CD45RO+ T lumphocyte subpopulations

Mostafa Nokta, Robert Rossero, Joan Nichols, Mark Rosenbaum, Richard B Pollard

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The effect of aggressive antiretroviral therapy on spontaneous apoptosis (AP) in CD4+ and CD8+ lymphocytes expressing CD45RO (memory cells) and CD45RA (naive cells) and their relationship to cellular activation and viral load were examined. Ten patients receiving simultaneous treatment with d4T, ddI, and HU were evaluated. Flow cytometric analysis showed significant levels of AP (measured by TUNEL assay) among memory and naive T cells and an enhanced expression of CD38 and HLA-DR activation markers. The percentage of apoptotic CD4+CD45RO+ and CD4+CD45RA+ cells decreased, respectively, from 34 ± 3.3 and 29 ± 3.6 prior to treatment to 20.5 ± 4 and 22 ± 3.8 at week 8 into therapy. The percentage of apoptotic CD8+CD45RO+ and CD8+CD45RA+ cells similarly decreased, respectively, from 20 ± 2.5 and 24 ± 3 prior to treatment to 14.5 ± 2.7 and 16 ± 3 at week 8 into treatment. The percentage of CD4+ cells expressing the activation markers CD38 and HLA-DR decreased from 27 ± 6 to 13 ± 2 and from 26 ± 4 to 13.5 ± 3, respectively. The percentage of CD8+ cells expressing either CD38 or HLA-DR fell from 22 ± 3 to 10 ± 2 for the former and from 39 ± 5 to 22 ± 4 for the latter. This was associated with a significant decrease in viral load (mean, 1.4 log10), and a decline in circulating plasma TNF-α and sIL-2R levels from 50.5 ± 10 to 21 ± 6 and 92.5 ± 11 to 68 ± 9, respectively. These data indicate that short-term therapy with ddI, d4T, and HU in combination diminished AP, immune activation, and partially restored naive and memory T cell subpopulations.

Original languageEnglish (US)
Pages (from-to)255-264
Number of pages10
JournalAIDS Research and Human Retroviruses
Volume15
Issue number3
DOIs
StatePublished - Feb 10 1999
Externally publishedYes

Fingerprint

Stavudine
Didanosine
Hydroxyurea
Apoptosis
HLA-DR Antigens
Viral Load
Therapeutics
T-Lymphocytes
In Situ Nick-End Labeling
Lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Effect of didanosine, stavudine, and hydroxyurea therapy on apoptosis in CD45RA+ and CD45RO+ T lumphocyte subpopulations. / Nokta, Mostafa; Rossero, Robert; Nichols, Joan; Rosenbaum, Mark; Pollard, Richard B.

In: AIDS Research and Human Retroviruses, Vol. 15, No. 3, 10.02.1999, p. 255-264.

Research output: Contribution to journalArticle

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abstract = "The effect of aggressive antiretroviral therapy on spontaneous apoptosis (AP) in CD4+ and CD8+ lymphocytes expressing CD45RO (memory cells) and CD45RA (naive cells) and their relationship to cellular activation and viral load were examined. Ten patients receiving simultaneous treatment with d4T, ddI, and HU were evaluated. Flow cytometric analysis showed significant levels of AP (measured by TUNEL assay) among memory and naive T cells and an enhanced expression of CD38 and HLA-DR activation markers. The percentage of apoptotic CD4+CD45RO+ and CD4+CD45RA+ cells decreased, respectively, from 34 ± 3.3 and 29 ± 3.6 prior to treatment to 20.5 ± 4 and 22 ± 3.8 at week 8 into therapy. The percentage of apoptotic CD8+CD45RO+ and CD8+CD45RA+ cells similarly decreased, respectively, from 20 ± 2.5 and 24 ± 3 prior to treatment to 14.5 ± 2.7 and 16 ± 3 at week 8 into treatment. The percentage of CD4+ cells expressing the activation markers CD38 and HLA-DR decreased from 27 ± 6 to 13 ± 2 and from 26 ± 4 to 13.5 ± 3, respectively. The percentage of CD8+ cells expressing either CD38 or HLA-DR fell from 22 ± 3 to 10 ± 2 for the former and from 39 ± 5 to 22 ± 4 for the latter. This was associated with a significant decrease in viral load (mean, 1.4 log10), and a decline in circulating plasma TNF-α and sIL-2R levels from 50.5 ± 10 to 21 ± 6 and 92.5 ± 11 to 68 ± 9, respectively. These data indicate that short-term therapy with ddI, d4T, and HU in combination diminished AP, immune activation, and partially restored naive and memory T cell subpopulations.",
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