Inhibition of the accessory function of murine macrophages in vitro by cyclosporine.
The accessory function of macrophages, which is strictly related to the induction of T cell activation, has been studied to determine whether it is affected by cyclosporine (CsA). Irradiated spleen cells, used as a source of macrophages, were pulsed overnight with beta-galactosidase (GZ) in the presence of CsA. After washing of the pulsed macrophages, cells from a GZ-specific T cell line were added to cultures and 3H-thymidine incorporation was measured 72 hr later. We found that 500 ng/ml CsA present during macrophage pulsing with GZ reduced T cell proliferation to 5%. On the other hand, 100 ng/ml CsA almost completely abrogated the proliferative response when present for the duration of the culture. Similar results were also obtained using antigen-pulsed peritoneal-adherent macrophages to stimulate the T cell line to proliferate, or a T hybridoma clone to produce interleukin-2 (IL-2). The possibility that CsA actually affects interleukin-1 (IL-1) production by macrophages by inhibiting uninvolved T cells could be ruled out. We conclude that CsA-induced inhibition of T cell functions (proliferation and IL-2 production) is partially due to the effect of the drug on the accessory function of macrophages. This immunosuppressive mechanism of action of CsA on macrophages has not been previously described.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D005696:Galactosidases / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D003524:Cyclosporins; D007375:Interleukin-1; D007376:Interleukin-2; D003609:Dactinomycin; D003513:Cycloheximide; D005696:Galactosidases