Deregulation of the CD95/CD95L system in lymphocytes from patients with primary acute HIV infection

Andrea Cossarizza, Gianna Stent, Cristina Mussini, Roberto Paganelli, Vanni Borghi, Cira Nuzzo, Marcello Pinti, Jessica Pedrazzi, Francesca Benatti, Roberto Esposito, Bård Røsok, Shigekazu Nagata, Stefano Vella, Claudio Franceschi, Bruno De Rienzo

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)345-355
Number of pages11
JournalAIDS (London, England)
Volume14
Issue number4
DOIs
Publication statusPublished - 2000

Fingerprint

Fas Ligand Protein
HIV Infections
Lymphocytes
Viral Load
Reverse Transcription
Flow Cytometry
Cell Membrane
Viruses
Polymerase Chain Reaction
Messenger RNA
Virus Diseases
Surface Antigens
Lymphocyte Activation
Natural Killer Cells
B-Lymphocytes
Cell Culture Techniques
Enzyme-Linked Immunosorbent Assay
Monoclonal Antibodies
HIV
RNA

Keywords

  • Acute HIV syndrome
  • Apoptosis
  • CD95
  • CD95L
  • HIV
  • Mitochondria

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Cossarizza, A., Stent, G., Mussini, C., Paganelli, R., Borghi, V., Nuzzo, C., ... De Rienzo, B. (2000). Deregulation of the CD95/CD95L system in lymphocytes from patients with primary acute HIV infection. AIDS (London, England), 14(4), 345-355. https://doi.org/10.1097/00002030-200003100-00007

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 journalArticle

Cossarizza, A, Stent, G, Mussini, C, Paganelli, R, Borghi, V, Nuzzo, C, Pinti, M, Pedrazzi, J, Benatti, F, Esposito, R, Røsok, B, Nagata, S, Vella, S, Franceschi, C & De Rienzo, B 2000, 'Deregulation of the CD95/CD95L system in lymphocytes from patients with primary acute HIV infection', AIDS (London, England), vol. 14, no. 4, pp. 345-355. https://doi.org/10.1097/00002030-200003100-00007
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. / Deregulation of the CD95/CD95L system in lymphocytes from patients with primary acute HIV infection. In: AIDS (London, England). 2000 ; Vol. 14, No. 4. pp. 345-355.
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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

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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.

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