GALLIUM-ARSENIDE SELECTIVELY INHIBITS T-CELL PROLIFERATION AND ALTERSEXPRESSION OF CD25 (IL-2R P55)

Exposure (24 hr) to a single intratracheal administration of gallium a rsenide (GaAs; 200 mg/kg) has been shown to suppress antibody producti on as well as other T cell-mediated immunological functions. GaAs has also been shown to exert toxic effects on events occurring early in th e antibody-forming cell response which may include lymphocyte activati on and proliferation. Studies were undertaken to determine whether GaA s exposure resulted in the inability of T and B lymphocytes to prolife rate in response to an antigenic stimulus. During the first 24 hr afte r in vitro immunization with sheep red blood cells, GaAs-exposed splen ocytes were suppressed 51% in their ability to proliferate compared to the vehicle (0.05% Tween 80 in saline; VH) control. There was no sign ificant difference in absolute numbers of cluster designation (CD)8+ c ells between VH- and GaAs-exposed cultures. There was, however, a 50% decrease in CD4+ cells evaluated 24 hr after immunization with sheep r ed blood cells which persisted for the 5-day culture period. T and B c ells were isolated and analyzed for proliferative capacity in response to various mitogenic stimuli. Isolated B cells exhibited no differenc e between VH- and GaAs-exposed cells in proliferative capacity to eith er lipopolysaccharide or anti-immunoglobulin plus interleukin-4. Howev er, isolated T cells exposed to GaAs were significantly suppressed in their ability to proliferate to concanavalin A, phytohemagglutinin and anti-CD3epsilon plus interleukin-2 when compared to VH. In addition, expression of CD25, leukocyte function antigen-1 and intercellular adh esion molecule-1 in GaAs-exposed mice were significantly below VH (36, 18 and 18%, respectively). Although expression of these molecules was upregulated by T cell receptor and interleukin-2 stimulation, a level of expression equal to VH was never obtained. These data indicate tha t GaAs selectively inhibits T cell proliferation, possibly by interfer ing with primary and secondary signals involved in mitogenic and antig en-driven responses.