Dynamic correlation of apoptosis and immune activation during treatment of HIV infection


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Dynamic correlation of apoptosis and immune activation during treatment of HIV infection
Cell Death and Differentiation
Bradley  A. D., Parato  K., Cameron  D. W., Kravcik  S., Phenix  B. N., Ashby  D., Kumar  A., Lynch  D. H., Tschopp  J., Angel  J. B.
1350-9047 (Print)
Statut éditorial
Date de publication
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
T cells from HIV infected patients undergo spontaneous apoptosis at a faster rate than those from uninfected patients, are abnormally susceptible to activation induced cell death (AICD), and undergo increased apoptosis in response to Fas receptor ligation. These observations have led to the hypothesis CD4 T cell apoptosis may be a mechanism of CD4 T cell depletion and the pathogenesis of AIDS. Successful treatment of HIV infected patients is accompanied by quantitative and qualitative improvements in immune function reflecting at least partial reversibility of the underlying pathogenesis of HIV. In this report we correlate improvements in markers of immune function with a decrease in apoptosis, and changes in its regulation. Therapy with nelfinavir plus saquinavir in combination with two nucleoside analogue inhibitors of reverse transcriptase dramatically reduces plasma viremia and increases CD4 T cell counts. Coincident with these improvements, CD38 and HLA-DR coexpression on both CD4 and CD8 T cells decrease, and CD45RA and CD62L coexpression increase. Furthermore, spontaneous apoptosis decreases in both CD4 and CD8 T cells (CD4 apoptosis 17.4 vs 2.6%, P=0.005; CD8 apoptosis 15.0 vs 1.0%, P<0.001), as does both Fas mediated apoptosis (CD4 apoptosis 19.0 vs 3.5%, P=0.03; CD8 apoptosis 13.7 vs 1.5%, P=0.002) and CD3 induced AICD (CD4 apoptosis 13.7 vs 3.2%, P=0.001; CD8 apoptosis 29 vs 2.2%, P=0.08). Changes in apoptosis are not associated with changes in Fas receptor expression, but are significantly correlated with changes in activation marker profiles. Although this suggests a possible regulatory role for the apoptosis inhibitory protein FLIP, direct assessment did not reveal quantitative differences in FLIP expression between apoptosis resistant PBL's from HIV negative patients, and apoptosis sensitive PBL's from HIV positive patients. These findings support the hypothesis that apoptosis mediates HIV induced CD4 T cell depletion, but indicate the need for further studies into the molecular regulation of HIV induced apoptosis.
Adolescent Adult Anti-HIV Agents/therapeutic use Antigens, CD95/biosynthesis *Apoptosis CASP8 and FADD-Like Apoptosis Regulating Protein Carrier Proteins/biosynthesis Drug Therapy, Combination HIV Infections/*drug therapy/*immunology/virology HIV Protease Inhibitors/therapeutic use Humans *Intracellular Signaling Peptides and Proteins Middle Aged Nelfinavir/therapeutic use Nucleosides/therapeutic use Reverse Transcriptase Inhibitors/therapeutic use Saquinavir/therapeutic use T-Lymphocytes/immunology
Web of science
Open Access
Création de la notice
24/01/2008 16:18
Dernière modification de la notice
08/05/2019 22:11
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