Dissection of defective antigen presentation by interferon-gamma-treated fibroblasts.
The capacity of interferon-gamma (IFN-gamma)-treated HLA-DR expressing human dermal fibroblasts (FB) to function as antigen-presenting cells (APC) was examined. FB were cultured with 250 U/ml IFN-gamma for 4 days to induce HLA-DR expression. Peripheral blood monocytes (M phi), FB, or IFN-gamma-treated FB from the same donor were then cultured overnight with or without the recall antigen streptokinase streptodornase (SKSD), and their capacity to stimulate autologous T4 cell DNA synthesis was examined. SKSD-bearing M phi stimulated T4 cell proliferation, whereas antigen-bearing HLA-DR (+) FB did not. Even after fixation with paraformaldehyde to eliminate metabolic activity, SKSD-bearing M phi, but not FB, were able to function as APC. However, when HLA-DR (-) endothelial cell (EC) or autologous or HLA-D-mismatched M phi were added to the cultures, antigen-pulsed IFN-gamma-treated FB and M phi were comparably effective stimulators of autologous T4 cell DNA synthesis. Antigen recognition by the T4 cell was restricted by the class II major histocompatibility complex (MHC)-encoded gene products expressed by the IFN-gamma-treated FB and was unrelated to the class I or II MHC-encoded gene products expressed by the additional cell type. EC-promoted T4 cell DNA synthesis induced by antigen-bearing IFN-gamma-treated FB was inhibited by 60.3, a monoclonal antibody directed at an epitope common to LFA-1, CR3, and the p150,95 molecule. Inhibition caused by 60.3 was completely reversed by the addition of IL 2 to the cultures. Antigen presentation by IFN-gamma-treated FB was also enhanced somewhat by IL 1, IL 2, or monoclonal antibody directed at Tp44 (9.3). However, each of these additions alone promoted T cell proliferation less effectively than EC and resulted in responses that were smaller than those triggered by antigen-bearing M phi. The data suggest that IFN-gamma-treated FB take up and process antigen effectively, but lack an accessory cell property necessary for antigen-induced T4 cell IL 2 production and proliferation.
D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D004727:Endothelium / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology*; D005404:Fixatives; D005557:Formaldehyde; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology; D011108:Polymers; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D005404:Fixatives; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007376:Interleukin-2; D011108:Polymers; D005557:Formaldehyde; D007371:Interferon-gamma; C003043:paraform