Initiation of antiretroviral therapy during primary HIV-1 infection induces rapid stabilization of the T-cell receptor beta chain repertoire and reduces the level of T-cell oligoclonality

Details

Serval ID
serval:BIB_9BF24D6C52A7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Initiation of antiretroviral therapy during primary HIV-1 infection induces rapid stabilization of the T-cell receptor beta chain repertoire and reduces the level of T-cell oligoclonality
Journal
Blood
Author(s)
Soudeyns  H., Campi  G., Rizzardi  G. P., Lenge  C., Demarest  J. F., Tambussi  G., Lazzarin  A., Kaufmann  D., Casorati  G., Corey  L., Pantaleo  G.
ISSN
0006-4971 (Print)
Publication state
Published
Issued date
03/2000
Volume
95
Number
5
Pages
1743-51
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Mar 1
Abstract
Major T-cell receptor beta chain variable region (TCRBV) repertoire perturbations are temporally associated with the down-regulation of viremia during primary human immunodeficiency virus (HIV) infection and with oligoclonal expansion and clonal exhaustion of HIV-specific cytotoxic T lymphocytes (CTLs). To determine whether initiation of antiretroviral therapy (ART) or highly active antiretroviral therapy (HAART) during primary infection influences the dynamics of T-cell-mediated immune responses, the TCRBV repertoire was analyzed by semiquantitative polymerase chain reaction in serial blood samples obtained from 11 untreated and 11 ART-treated patients. Repertoire variations were evaluated longitudinally. Stabilization of the TCRBV repertoire was more consistently observed in treated as compared with untreated patients. Furthermore, the extent and the rapidity of stabilization were significantly different in treated versus untreated patients. TCRBV repertoire stabilization was positively correlated with the slope of HIV viremia in the treated group, suggesting an association between repertoire stabilization and virologic response to treatment. To test whether stabilization was associated with variations in the clonal complexity of T-cell populations, T-cell receptor (TCR) heteroduplex mobility shift assays (HMAs) were performed on sequential samples from 4 HAART-treated subjects. Densitometric analysis of HMA profiles showed a reduction in the number of TCR clonotypes in most TCRBV families and a significant decrease in the total number of clonotypes following 7 months of HAART. Furthermore, a biphasic decline in HIV-specific but not heterologous CTL clones was observed. This indicates that ART leads to a global reduction of CD8(+) T-cell oligoclonality and significantly modulates the mobilization of HIV-specific CTL during primary infection. (Blood. 2000;95:1743-1751)
Keywords
Acute Disease Anti-HIV Agents/*administration & dosage/pharmacology Clone Cells/immunology Didanosine/administration & dosage/pharmacology Drug Administration Schedule Drug Therapy, Combination *Gene Rearrangement, beta-Chain T-Cell Antigen Receptor HIV Infections/*drug therapy/immunology HIV Protease Inhibitors/administration & dosage/pharmacology *Hiv-1 HIV-1 Reverse Transcriptase/antagonists & inhibitors Humans Indinavir/administration & dosage/pharmacology Lamivudine/administration & dosage/pharmacology *Lymphocyte Activation Polymerase Chain Reaction RNA-Directed DNA Polymerase/administration & dosage/pharmacology Saquinavir/administration & dosage/pharmacology T-Lymphocytes, Cytotoxic/*drug effects/immunology Viremia/*drug therapy/immunology Zidovudine/administration & dosage/pharmacology
Pubmed
Web of science
Create date
25/01/2008 16:13
Last modification date
20/08/2019 16:02
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