The B lymphocyte is the immune cell target for 2′,3′-dideoxyadenosine

Abstract

2′,3′-Dideoxyadenosine (ddA) is a nucleoside analogue with anti-HIV activity and one of its metabolic products, 2′,3′-dideoxyinosine (ddI), has shown promising results in clinical trials for the treatment of acquired immunodeficiency syndrome (AIDS). Because AIDS viruses target the immune system, it is important to understand the potential effects of anti-AIDS drugs, including natural nucleosides, on the immune system. Previous immunotoxicological studies have shown that 22 treatments with ddA to female B6C3F1 mice over a period of 30 days had no effect on cell-mediated immunity, including the mixed lymphocyte reaction and response to mitogenic signals, but suppressed the in vitro IgM plaque-forming cell (PFC) response to sheep red blood cells. The present studies show that suppression of the IgM PFC response was dose dependent with a 96% reduction in IgM PFCs 10 6 spleen cells at the highest dose (350 mg/kg). The in vivo IgM PFC response to DNP-Ficoll and the in vitro IgM PFC response to lipopolysaccharide, both T-independent antigens, were also suppressed in the spleens of ddA-treated mice. The analysis of splenocyte subtypes shows no change in the percentage of B cells (surface immunoglobulin positive cells), T helper cells (L3T4 positive cells), and T suppressor cells or T cytotoxic cells (Lyt-2 positive cells) in the spleens of ddA-treated mice. In vitro separation and reconstitution studies in which the IgM PFC response was monitored indicated that the B lymphocyte rather than the T lymphocyte or antigen-presenting cell is the primary cell targeted by ddA. This information provides a data base for further mechanistic study and may reflect on the clinical use of other nucleoside analogues, e.g., ddI by providing the clinician with information indicating the potential decrease in humoral immunity.