|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1743-1751
Initiation of antiretroviral therapy during primary HIV-1
infection induces rapid stabilization of the T-cell receptor  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, and
Giuseppe Pantaleo
From the Laboratory of AIDS Immunopathogenesis, Division of
Infectious Diseases, Department of Internal Medicine, Centre
Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Unit of
Immunochemistry, DIBIT, and the Department of Infectious
Diseases, San Raffaele Scientific Institute, Milan,
Italy; Duke University Medical Center, Center for AIDS Research,
Durham, NC; Fred Hutchinson Cancer Research Center, Seattle, WA 98105.
Major T-cell receptor  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.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. C. Simons, S. E. VanCompernolle, R. M. Smith, J. Wei, L. Barnett, S. L. Lorey, D. Meyer-Olson, and S. A. Kalams
Despite Biased TRBV Gene Usage against a Dominant HLA B57-Restricted Epitope, TCR Diversity Can Provide Recognition of Circulating Epitope Variants
J. Immunol.,
October 1, 2008;
181(7):
5137 - 5146.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Yang, T. Dong, E. Turnbull, S. Ranasinghe, B. Ondondo, N. Goonetilleke, N. Winstone, K. di Gleria, P. Bowness, C. Conlon, et al.
Broad TCR Usage in Functional HIV-1-Specific CD8+ T Cell Expansions Driven by Vaccination during Highly Active Antiretroviral Therapy
J. Immunol.,
July 1, 2007;
179(1):
597 - 606.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Lichterfeld, X. G. Yu, S. K. Mui, K. L. Williams, A. Trocha, M. A. Brockman, R. L. Allgaier, M. T. Waring, T. Koibuchi, M. N. Johnston, et al.
Selective Depletion of High-Avidity Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ T Cells after Early HIV-1 Infection
J. Virol.,
April 15, 2007;
81(8):
4199 - 4214.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hosmalin and P. Lebon
Type I interferon production in HIV-infected patients
J. Leukoc. Biol.,
November 1, 2006;
80(5):
984 - 993.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Meyer-Olson, K. W. Brady, M. T. Bartman, K. M. O'Sullivan, B. C. Simons, J. A. Conrad, C. B. Duncan, S. Lorey, A. Siddique, R. Draenert, et al.
Fluctuations of functionally distinct CD8+ T-cell clonotypes demonstrate flexibility of the HIV-specific TCR repertoire
Blood,
March 15, 2006;
107(6):
2373 - 2383.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Zhou, R. Ou, L. Huang, G. E. Price, and D. Moskophidis
Differential Tissue-Specific Regulation of Antiviral CD8+ T-Cell Immune Responses during Chronic Viral Infection
J. Virol.,
April 1, 2004;
78(7):
3578 - 3600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E Hodges, M T Krishna, C Pickard, and J L Smith
Diagnostic role of tests for T cell receptor (TCR) genes
J. Clin. Pathol.,
January 1, 2003;
56(1):
1 - 11.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Gorochov, A. U. Neumann, C. Parizot, T. Li, C. Katlama, and P. Debre
Down-regulation of CD8+ T-cell expansions in patients with human immunodeficiency virus infection receiving highly active combination therapy
Blood,
March 15, 2001;
97(6):
1787 - 1795.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Schito, E. Vittinghoff, F. M. Hecht, M. K. Elkins, J. O. Kahn, J. A. Levy, and J. R. Oksenberg
Longitudinal analysis of T-cell receptor gene use by CD8+ T cells in early human immunodeficiency virus infection in patients receiving highly active antiretroviral therapy
Blood,
January 1, 2001;
97(1):
214 - 220.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
