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

Objective: To analyze the role of CD95/CD95 ligand (CD95L) expression and f unctionality in peripheral blood lymphocytes (PBL) during primary, acute HI V 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 Cr-51 release and flow cytometry were used to evaluate cell killing via CD95 molecule, flow c ytometry to assess surface antigens, enzyme-linked immunosorbent assay (ELI SA) for the determination of soluble CD95 and CD95L plasma levels, quantita tive competitive (QC) reverse transcription polymerase chain reaction (RT-P CR) with an original RNA competitor for the analysis of CD95L mRNA expressi on and QC RT-PCR for determining plasma viral load. Results: The analysis of PBL during this phase revealed that almost all cel ls, including CD8 T cells with a virgin phenotype, B lymphocytes and natura l killer cells displayed CD95 molecules on the plasma membrane. Activation of CD95 on the surface of isolated lymphocytes by anti-CD95 monoclonal anti bodies 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 le vels, 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 t he plasma did not correlate with the plasma viral load, which varied widely from patient to patient. Further, plasma levels of soluble CD95 were not a ltered by decreased lymphocyte activation or by efficient antiretroviral th erapy. Conclusions: In patients experiencing an acute, primary HIV infection, a pr olonged deregulation of the CD95/CD95L system may exist, which is probably not entirely related to virus production but may contribute to the pathogen esis of the disease. The hypothesis can be put forward that a complex balan ce exists between proapoptotic events (increase in CD95 expression), probab ly triggered by the host as a method to limit viral production, and antiapo ptotic events (decrease in CD95L expression) probably triggered by the viru s as a way to increase its production and survival. (C) 2000 Lippincott Wil liams by Wilkins.