Abstract
Objective: To analyze the role of CD95/CD95 ligand (CD95L) expression and functionality in peripheral blood lymphocytes (PBL) during primary, acute HIV syndrome (AHS) and in the subsequent period. Patients: Twelve patients were studied during the acute phase of the viral infection and most were followed for some months. Methods: Cell culture and cytotoxicity assays based upon 51Cr release and flow cytometry were used to evaluate cell killing via CD95 molecule, flow cytometry to assess surface antigens, enzyme-linked immunosorbent assay (ELISA) for the determination of soluble CD95 and CD95L plasma levels, quantitative competitive (QC) reverse transcription polymerase chain reaction (RT-PCR) with an original RNA competitor for the analysis of CD95L mRNA expression and QC RT-PCR for determining plasma viral load. Results: The analysis of PBL during this phase revealed that almost all cells, including CD8 T cells with a virgin phenotype, B lymphocytes and natural killer cells displayed CD95 molecules on the plasma membrane. Activation of CD95 on the surface of isolated lymphocytes by anti-CD95 monoclonal antibodies or binding to CD95L induced rapid apoptosis. However, CD95L mRNA was not expressed in PBL from these patients and was poorly inducible. Soluble CD95 was found in the plasma of all patients, but only in a few at high levels, even some months after seroconversion. In contrast, soluble CD95L was detected in only one patient, this occurring after the symptomatic period. For 10 of the 12 patients, expression of CD95 on the cell membrane or in the plasma did not correlate with the plasma viral load, which varied widely from patient to patient. Further, plasma levels of soluble CD95 were not altered by decreased lymphocyte activation or by efficient antiretroviral therapy. Conclusions: In patients experiencing an acute, primary HIV infection, a prolonged deregulation of the CD95/CD95L system may exist, which is probably not entirely related to virus production but may contribute to the pathogenesis of the disease. The hypothesis can be put forward that a complex balance exists between proapoptotic events (increase in CD95 expression), probably triggered by the host as a method to limit viral production, and antiapoptotic events (decrease in CD95L expression) probably triggered by the virus as a way to increase its production and survival. (C) 2000 Lippincott Williams and Wilkins.
| Original language | English |
|---|---|
| Pages (from-to) | 345-355 |
| Number of pages | 11 |
| Journal | AIDS (London, England) |
| Volume | 14 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2000 |
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Keywords
- Acute HIV syndrome
- Apoptosis
- CD95
- CD95L
- HIV
- Mitochondria
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Deregulation of the CD95/CD95L system in lymphocytes from patients with primary acute HIV infection. / Cossarizza, Andrea; Stent, Gianna; Mussini, Cristina; Paganelli, Roberto; Borghi, Vanni; Nuzzo, Cira; Pinti, Marcello; Pedrazzi, Jessica; Benatti, Francesca; Esposito, Roberto; Røsok, Bård; Nagata, Shigekazu; Vella, Stefano; Franceschi, Claudio; De Rienzo, Bruno.
In: AIDS (London, England), Vol. 14, No. 4, 2000, p. 345-355.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Deregulation of the CD95/CD95L system in lymphocytes from patients with primary acute HIV infection
AU - Cossarizza, Andrea
AU - Stent, Gianna
AU - Mussini, Cristina
AU - Paganelli, Roberto
AU - Borghi, Vanni
AU - Nuzzo, Cira
AU - Pinti, Marcello
AU - Pedrazzi, Jessica
AU - Benatti, Francesca
AU - Esposito, Roberto
AU - Røsok, Bård
AU - Nagata, Shigekazu
AU - Vella, Stefano
AU - Franceschi, Claudio
AU - De Rienzo, Bruno
PY - 2000
Y1 - 2000
N2 - Objective: To analyze the role of CD95/CD95 ligand (CD95L) expression and functionality in peripheral blood lymphocytes (PBL) during primary, acute HIV syndrome (AHS) and in the subsequent period. Patients: Twelve patients were studied during the acute phase of the viral infection and most were followed for some months. Methods: Cell culture and cytotoxicity assays based upon 51Cr release and flow cytometry were used to evaluate cell killing via CD95 molecule, flow cytometry to assess surface antigens, enzyme-linked immunosorbent assay (ELISA) for the determination of soluble CD95 and CD95L plasma levels, quantitative competitive (QC) reverse transcription polymerase chain reaction (RT-PCR) with an original RNA competitor for the analysis of CD95L mRNA expression and QC RT-PCR for determining plasma viral load. Results: The analysis of PBL during this phase revealed that almost all cells, including CD8 T cells with a virgin phenotype, B lymphocytes and natural killer cells displayed CD95 molecules on the plasma membrane. Activation of CD95 on the surface of isolated lymphocytes by anti-CD95 monoclonal antibodies or binding to CD95L induced rapid apoptosis. However, CD95L mRNA was not expressed in PBL from these patients and was poorly inducible. Soluble CD95 was found in the plasma of all patients, but only in a few at high levels, even some months after seroconversion. In contrast, soluble CD95L was detected in only one patient, this occurring after the symptomatic period. For 10 of the 12 patients, expression of CD95 on the cell membrane or in the plasma did not correlate with the plasma viral load, which varied widely from patient to patient. Further, plasma levels of soluble CD95 were not altered by decreased lymphocyte activation or by efficient antiretroviral therapy. Conclusions: In patients experiencing an acute, primary HIV infection, a prolonged deregulation of the CD95/CD95L system may exist, which is probably not entirely related to virus production but may contribute to the pathogenesis of the disease. The hypothesis can be put forward that a complex balance exists between proapoptotic events (increase in CD95 expression), probably triggered by the host as a method to limit viral production, and antiapoptotic events (decrease in CD95L expression) probably triggered by the virus as a way to increase its production and survival. (C) 2000 Lippincott Williams and Wilkins.
AB - Objective: To analyze the role of CD95/CD95 ligand (CD95L) expression and functionality in peripheral blood lymphocytes (PBL) during primary, acute HIV syndrome (AHS) and in the subsequent period. Patients: Twelve patients were studied during the acute phase of the viral infection and most were followed for some months. Methods: Cell culture and cytotoxicity assays based upon 51Cr release and flow cytometry were used to evaluate cell killing via CD95 molecule, flow cytometry to assess surface antigens, enzyme-linked immunosorbent assay (ELISA) for the determination of soluble CD95 and CD95L plasma levels, quantitative competitive (QC) reverse transcription polymerase chain reaction (RT-PCR) with an original RNA competitor for the analysis of CD95L mRNA expression and QC RT-PCR for determining plasma viral load. Results: The analysis of PBL during this phase revealed that almost all cells, including CD8 T cells with a virgin phenotype, B lymphocytes and natural killer cells displayed CD95 molecules on the plasma membrane. Activation of CD95 on the surface of isolated lymphocytes by anti-CD95 monoclonal antibodies or binding to CD95L induced rapid apoptosis. However, CD95L mRNA was not expressed in PBL from these patients and was poorly inducible. Soluble CD95 was found in the plasma of all patients, but only in a few at high levels, even some months after seroconversion. In contrast, soluble CD95L was detected in only one patient, this occurring after the symptomatic period. For 10 of the 12 patients, expression of CD95 on the cell membrane or in the plasma did not correlate with the plasma viral load, which varied widely from patient to patient. Further, plasma levels of soluble CD95 were not altered by decreased lymphocyte activation or by efficient antiretroviral therapy. Conclusions: In patients experiencing an acute, primary HIV infection, a prolonged deregulation of the CD95/CD95L system may exist, which is probably not entirely related to virus production but may contribute to the pathogenesis of the disease. The hypothesis can be put forward that a complex balance exists between proapoptotic events (increase in CD95 expression), probably triggered by the host as a method to limit viral production, and antiapoptotic events (decrease in CD95L expression) probably triggered by the virus as a way to increase its production and survival. (C) 2000 Lippincott Williams and Wilkins.
KW - Acute HIV syndrome
KW - Apoptosis
KW - CD95
KW - CD95L
KW - HIV
KW - Mitochondria
UR - http://www.scopus.com/inward/record.url?scp=0034030616&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034030616&partnerID=8YFLogxK
U2 - 10.1097/00002030-200003100-00007
DO - 10.1097/00002030-200003100-00007
M3 - Article
C2 - 10770536
AN - SCOPUS:0034030616
VL - 14
SP - 345
EP - 355
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 4
ER -