Gallium arsenide selectively suppresses antigen processing by splenic macrophages for CD4+ T cell activation.
Gallium arsenide (GaAs) is an intermetallic compound used in the electronics industry as a semiconductor. Acute exposure of animals to GaAs suppresses various immune functions. We investigated the effects of GaAs on immunocompetency with emphasis on macrophages. Mice were given 12.5 to 200 mg/kg GaAs i.p., and immune parameters were examined 1 or 5 days later. Chemically exposed mice did not display alteration in spienic cellular composition. Despite this, primary in vitro humoral response to sheep red blood cells by GaAs-exposed mice was inhibited in a dose-dependent manner. The ability of 5-day vehicle- or 200 mg/kg GaAs-exposed splenic macrophages to induce interleukin-2 production by antigen-specific CD4+ helper T cell hybridomas stimulated with soluble protein antigens was assessed. GaAs-exposed macrophages were less competent in eliciting T cell responses to pigeon cytochrome c and pork insulin than vehicle-exposed cells. However, GaAs-exposed macrophages activated hen egg lysozyme- and chicken ovalbumin-specific T cells as efficiently as vehicle control cells. Also, suppressed processing of cytochrome c was not observed after a 1-day exposure. Chemical exposure did not alter the expression of major histocompatibility complex class II molecules on the macrophages or their activation of T cells by peptides, which do not require processing. Therefore, GaAs causes a time- and antigen-dependent defect in antigen processing that is essential for CD4+ T cell stimulation by splenic macrophages.
Lewis
T A
TA
Department of Microbiology, Medical College of Virginia/Virginia Commonwealth University, Richmond, USA.
Munson
A E
AE
McCoy
K L
KL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects*; D001152:Arsenicals / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005708:Gallium / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006825:Hybridomas; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D010455:Peptides / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013997:Time Factors
D001152:Arsenicals; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D010455:Peptides; C043055:gallium arsenide; D005708:Gallium