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

Hugo Soudeyns, Gabriele Campi, G. Paolo Rizzardi, Caterina Lenge, James F. Demarest, Giuseppe Tambussi, Adriano Lazzarin, Daniel Kaufmann, Giulia Casorati, Lawrence Corey, Giuseppe Pantaleo

Research output: Contribution to journalArticle

Abstract

Major T-cell receptor β chain variable region (TCRBV) repertoire perturbations are temporally associated with the downregulation 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. (C) 2000 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)1743-1751
Number of pages9
JournalBlood
Volume95
Issue number5
Publication statusPublished - Mar 1 2000

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Initiation of antiretroviral therapy during primary HIV-1 infection induces rapid stabilization of the T-cell receptor β chain repertoire and reduces the level of T-cell oligoclonality'. Together they form a unique fingerprint.

  • Cite this

    Soudeyns, H., Campi, G., Rizzardi, G. P., Lenge, C., Demarest, J. F., Tambussi, G., Lazzarin, A., Kaufmann, D., Casorati, G., Corey, L., & Pantaleo, G. (2000). Initiation of antiretroviral therapy during primary HIV-1 infection induces rapid stabilization of the T-cell receptor β chain repertoire and reduces the level of T-cell oligoclonality. Blood, 95(5), 1743-1751.