Immunomodulation of in vitro antigen presentation by cations.
The ability of various cations to alter an antigen-specific (ovalbumin) T cell activation system in vitro has been assessed. This in vitro system includes analysis of antigen capture, processing, and presentation by antigen presenting cells (APC) (splenocytes, B cells or macrophages) in a major histocompatibility complex (MHC) restricted fashion and the evaluation of the activation of a T-cell hybridoma, DO-11.10, which is specific for "processed" ovalbumin in association with I-Ad. Activation is determined by production of IL2 which is quantitated in a bioassay with HT-2 cells. Numerous metals (10 and 100 microM) were screened in the coculture assay (APC and DO-11.10 plus ovalbumin). Metals with inhibitory effects were Cd greater than Cu greater than Pb greater than Zn. Co and Cr had no modulatory effect and Ni had an enhancing effect (increased IL2 production). The effects of the modulatory metals were further assessed for influences on the individual cellular components of this system. Cd was toxic to all cell types whereas Cu was toxic only to irradiated splenocytes and Do-11.10. Pb was the only metal which was not toxic to any cell type but still inhibited antigen presentation. To prevent influences of metals on DO-11.10 or carryover into the bioassay, APC were preincubated with metals and then assessed for presentation capability. After preincubation, only Cd, Pb, and Cu were inhibitory. The inhibition by Cd was due to toxicity. Cu inhibited only irradiated splenocyte presentation and this effect was due to toxicity. Pb inhibition was due to a mechanism other than toxicity and its biochemical influences on APC are discussed.
Smith
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KL
Department of Microbiology and Immunology, Albany Medical College, New York 12208.
Lawrence
D A
DA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000633:toxicity; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D007854:Lead / Q000633:toxicity; D008213:Lymphocyte Activation / Q000187:drug effects; D008670:Metals / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009532:Nickel / Q000633:toxicity
D007376:Interleukin-2; D008670:Metals; D007854:Lead; D003300:Copper; D009532:Nickel