Abstract
Objective: The influence of structured treatment interruption on effector/memory CD8 T cell dynamics was analysed in chronic HIV-infected patients showing a rapid or delayed viral rebound. Design: Structured treatment interruption consisted of at least one month of discontinuation, followed by highly active antiretroviral therapy (HAART) resumption. Two groups of HIV structured treatment interruption patients were selected on the basis of plasma viral HIV-RNA value (> 30 000 copies/ml, branched DNA): group A (n = 14), patients with a rapid viral rebound (within one month) and group B (n = 6), patients with a delayed or no viral rebound (after a minimum of 4 months). Methods: A clinical and immunological follow-up was performed at HAART suspension (t 0), one month from suspension (t 1), at HAART resumption (t 2), and 30 days from resumption (t 3). Results: A sustained viral rebound was observed in group A patients, showing a rapid expansion of circulating CD8 T lymphocytes. In this group, the frequencies of CD8 T cells releasing IFN-γ after mitogen-induced or Gag-specific stimulation were highly increased after HAART discontinuation. Nevertheless, these CD8 T lymphocytes were mainly composed of pre-terminally differentiated cytotoxic T lymphocytes (CTL) expressing a CCR7- CD27+/- CD45RA- phenotype and a reduced amount of perforin. In contrast, group B patients showed no significant changes in immunological parameters during a prolonged drug-free period. Conclusion: These data indicate that monitoring CD8 T cell dynamics during structured treatment interruption could be clinically relevant, and new therapeutic strategies should aim qualitatively to restore CTL effector functions.
| Original language | English |
|---|---|
| Pages (from-to) | 2431-2438 |
| Number of pages | 8 |
| Journal | AIDS (London, England) |
| Volume | 16 |
| Issue number | 18 |
| DOIs | |
| Publication status | Published - Dec 6 2002 |
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Keywords
- CCR7
- CD27
- CTL
- HAART
- HIV-1 Gag
- Peptides
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Expansion of pre-terminally differentiated CD8 T cells in chronic HIV-positive patients presenting a rapid viral rebound during structured treatment interruption. / D'Offizi, Gianpiero; Montesano, Carla; Agrati, Chiara; Gioia, Cristiana; Amicosante, Massimo; Topino, Simone; Narciso, Pasquale; Pucillo, Leopoldo Paolo; Ippolito, Giuseppe; Poccia, Fabrizio.
In: AIDS (London, England), Vol. 16, No. 18, 06.12.2002, p. 2431-2438.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expansion of pre-terminally differentiated CD8 T cells in chronic HIV-positive patients presenting a rapid viral rebound during structured treatment interruption
AU - D'Offizi, Gianpiero
AU - Montesano, Carla
AU - Agrati, Chiara
AU - Gioia, Cristiana
AU - Amicosante, Massimo
AU - Topino, Simone
AU - Narciso, Pasquale
AU - Pucillo, Leopoldo Paolo
AU - Ippolito, Giuseppe
AU - Poccia, Fabrizio
PY - 2002/12/6
Y1 - 2002/12/6
N2 - Objective: The influence of structured treatment interruption on effector/memory CD8 T cell dynamics was analysed in chronic HIV-infected patients showing a rapid or delayed viral rebound. Design: Structured treatment interruption consisted of at least one month of discontinuation, followed by highly active antiretroviral therapy (HAART) resumption. Two groups of HIV structured treatment interruption patients were selected on the basis of plasma viral HIV-RNA value (> 30 000 copies/ml, branched DNA): group A (n = 14), patients with a rapid viral rebound (within one month) and group B (n = 6), patients with a delayed or no viral rebound (after a minimum of 4 months). Methods: A clinical and immunological follow-up was performed at HAART suspension (t 0), one month from suspension (t 1), at HAART resumption (t 2), and 30 days from resumption (t 3). Results: A sustained viral rebound was observed in group A patients, showing a rapid expansion of circulating CD8 T lymphocytes. In this group, the frequencies of CD8 T cells releasing IFN-γ after mitogen-induced or Gag-specific stimulation were highly increased after HAART discontinuation. Nevertheless, these CD8 T lymphocytes were mainly composed of pre-terminally differentiated cytotoxic T lymphocytes (CTL) expressing a CCR7- CD27+/- CD45RA- phenotype and a reduced amount of perforin. In contrast, group B patients showed no significant changes in immunological parameters during a prolonged drug-free period. Conclusion: These data indicate that monitoring CD8 T cell dynamics during structured treatment interruption could be clinically relevant, and new therapeutic strategies should aim qualitatively to restore CTL effector functions.
AB - Objective: The influence of structured treatment interruption on effector/memory CD8 T cell dynamics was analysed in chronic HIV-infected patients showing a rapid or delayed viral rebound. Design: Structured treatment interruption consisted of at least one month of discontinuation, followed by highly active antiretroviral therapy (HAART) resumption. Two groups of HIV structured treatment interruption patients were selected on the basis of plasma viral HIV-RNA value (> 30 000 copies/ml, branched DNA): group A (n = 14), patients with a rapid viral rebound (within one month) and group B (n = 6), patients with a delayed or no viral rebound (after a minimum of 4 months). Methods: A clinical and immunological follow-up was performed at HAART suspension (t 0), one month from suspension (t 1), at HAART resumption (t 2), and 30 days from resumption (t 3). Results: A sustained viral rebound was observed in group A patients, showing a rapid expansion of circulating CD8 T lymphocytes. In this group, the frequencies of CD8 T cells releasing IFN-γ after mitogen-induced or Gag-specific stimulation were highly increased after HAART discontinuation. Nevertheless, these CD8 T lymphocytes were mainly composed of pre-terminally differentiated cytotoxic T lymphocytes (CTL) expressing a CCR7- CD27+/- CD45RA- phenotype and a reduced amount of perforin. In contrast, group B patients showed no significant changes in immunological parameters during a prolonged drug-free period. Conclusion: These data indicate that monitoring CD8 T cell dynamics during structured treatment interruption could be clinically relevant, and new therapeutic strategies should aim qualitatively to restore CTL effector functions.
KW - CCR7
KW - CD27
KW - CTL
KW - HAART
KW - HIV-1 Gag
KW - Peptides
UR - http://www.scopus.com/inward/record.url?scp=0037032905&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037032905&partnerID=8YFLogxK
U2 - 10.1097/00002030-200212060-00008
DO - 10.1097/00002030-200212060-00008
M3 - Article
C2 - 12461417
AN - SCOPUS:0037032905
VL - 16
SP - 2431
EP - 2438
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 18
ER -