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 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.