title: Immunosuppression by aldicarb of T cell responses to antigen-specific and polyclonal stimuli results from defective IL-1 production by the macrophages.
abstract: In the present study we investigated the immunomodulatory effects of aldicarb, a carbamate pesticide, on T cells activated by a number of different ways. When C3H mice were injected intraperitoneally with a single dose of Aldicarb, 0.005-50 micrograms/kg body wt, and their spleen cells were stimulated with T cell mitogens such as concanavalin A (ConA)3 or anti-CD3 monoclonal antibodies (mAb), a decreased responsiveness was detected when compared to the control mice. Aldicarb administered at concentrations less than 0.005 microgram/kg body wt failed to cause significant immunosuppression. Interestingly, when purified T cells from immunosuppressive doses of aldicarb-treated mice were stimulated with ConA in the presence of irradiated control macrophages, the defective T cell response was no longer demonstrable. Also, purified control T cells stimulated with ConA in the presence of irradiated macrophages from aldicarb-treated mice showed decreased responsiveness. Similar observations were made using anti-CD3 mAb to activate the T cells, inasmuch as whole spleen cells from aldicarb-treated mice showed decreased responsiveness to anti-CD3 stimulation, whereas purified T cells in the presence of irradiated control macrophages showed normal reactivity. The fact that aldicarb did not directly affect the T cell functions was further confirmed by stimulating purified T cells from aldicarb-treated mice with phorbol myristate acetate and calcium ionophore, a response which is independent of the accessory cells and which was found to be normal in aldicarb-treated mice. It was observed that the macrophages from aldicarb-treated mice demonstrated a decreased capacity to stimulate conalbumin-specific T helper cell clone, D10.G4, and when activated produced decreased amounts of IL-1 when compared to control macrophages. Also, the decreased stimulation of D10.G4 clone by aldicarb-treated macrophages was reconstituted when exogenous recombinant IL-1 was added to the cultures. These data together suggested that aldicarb affects the macrophage functions by interfering with IL-1 production and that it does not affect the T cell functions directly.
authors: Department of Biology, Virginia Polytechnic Institute and State University Blacksburg 24061.
authors: T N
authors: TN
authors: Dean
authors: V N
authors: VN
authors: Kakkanaiah
authors: M
authors: M
authors: Nagarkatti
authors: P S
authors: PS
authors: Nagarkatti
mesh_terms: D000448:Aldicarb / Q000633:toxicity*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D007165:Immunosuppression Therapy; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D007376:Interleukin-2; D008934:Mitogens; D000448:Aldicarb