Gallium arsenide selectively inhibits T cell proliferation and alters expression of CD25 (IL-2R/p55).
Exposure (24 hr) to a single intratracheal administration of gallium arsenide (GaAs; 200 mg/kg) has been shown to suppress antibody production as well as other T cell-mediated immunological functions. GaAs has also been shown to exert toxic effects on events occurring early in the antibody-forming cell response which may include lymphocyte activation and proliferation. Studies were undertaken to determine whether GaAs exposure resulted in the inability of T and B lymphocytes to proliferate in response to an antigenic stimulus. During the first 24 hr after in vitro immunization with sheep red blood cells, GaAs-exposed splenocytes were suppressed 51% in their ability to proliferate compared to the vehicle (0.05% Tween 80 in saline; VH) control. There was no significant difference in absolute numbers of cluster designation (CD)8+ cells between VH- and GaAs-exposed cultures. There was, however, a 50% decrease in CD4+ cells evaluated 24 hr after immunization with sheep red blood cells which persisted for the 5-day culture period. T and B cells were isolated and analyzed for proliferative capacity in response to various mitogenic stimuli. Isolated B cells exhibited no difference between VH- and GaAs-exposed cells in proliferative capacity to either lipopolysaccharide or anti-immunoglobulin plus interleukin-4. However, isolated T cells exposed to GaAs were significantly suppressed in their ability to proliferate to concanavalin A, phytohemagglutinin and anti-CD3 epsilon plus interleukin-2 when compared to VH. In addition, expression of CD25, leukocyte function antigen-1 and intercellular adhesion molecule-1 in GaAs-exposed mice were significantly below VH (36, 18 and 18%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Burns
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Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Munson
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D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D001152:Arsenicals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005708:Gallium / Q000633:toxicity*; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D001152:Arsenicals; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D008934:Mitogens; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1; C043055:gallium arsenide; D005708:Gallium; D001151:Arsenic