Non-specifically activated human peripheral blood mononuclear cells are cytotoxic for human keratinocytes in vitro.
Cultured human keratinocytes were lysed by activated PBMC in a 4-h 51Cr release assay. PBMC were activated by incubation with 50 U/ml of rIL-2 for 4 days. The cytotoxic precursors were found to be NKH1+ and included both CD2+ and CD2- phenotypes. This cytotoxicity was not genetically restricted, as cells killed both allogeneic and autologous keratinocytes without priming. Cytotoxicity was blocked by pre-incubation of effector cells with mAb against LFA-1 alpha-(TS1/22) and beta-chains (TS1/18), but not by antibodies directed against CD4, CD8, or leukocyte common Ag (T200) suggesting that LFA-1 is an important interactive molecule in this cytotoxicity. IFN-gamma is reported to upregulate ICAM-1, the ligand for LFA-1. Pre-treatment of target keratinocytes with IFN-gamma was also found to greatly increase the sensitivity of keratinocytes to lysis. This increased sensitivity to lysis was blocked by anti-LFA-1 and anti-ICAM-1, but not by anti-DR (L243), and thus was not the result of increased DR expression. Such treated targets were lysed at low levels (15 to 18%) by an Ag-specific CD8+ cytotoxic clone as well as a T cell line derived from a skin lesion of allergic contact dermatitis. In contrast, control keratinocytes were only sensitive to IL-2-activated PBMC as described above. The above findings may be relevant to a variety of conditions in which epidermal damage is associated with lymphocytic infiltrate. These conditions include graft-vs-host disease, erythema multiforme, and lupus erythematosus. DR+ keratinocytes, which may be a marker for IFN-gamma are also found in the above conditions. It is suggested that epidermal pathology may be mediated by non-specific cytotoxicity induced in the course of an immune response.
Kalish
R S
RS
Department of Dermatology, University of Minnesota Medical School, Minneapolis 55455.
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D001667:Binding, Competitive; D015815:Cell Adhesion Molecules; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D010641:Phenotype; D010835:Phytohemagglutinins; D013234:Stem Cells / Q000145:classification / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D000939:Epitopes; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D010835:Phytohemagglutinins; D007371:Interferon-gamma