Spontaneous diabetes mellitus in the Bio-Breeding/Worcester rat. Evidence in vitro for natural killer cell lysis of islet cells.
We sought direct evidence for anti-islet cellular cytotoxicity in diabetic Bio-Breeding/Worcester (BB/W) rats by comparing the effects of splenic lymphoid cells from BB/W diabetic (D), diabetes-prone (DP), and diabetes-resistant (DR) rats on the release of 51Cr from damaged islet cells in vitro. D and DP splenic lymphoid cells were cytotoxic to major histocompatibility complex (MHC)-compatible Wistar-Furth (WF) rat islet cells and also to MHC-incompatible Lewis rat islet cells and a rat islet cell line (RIN 5F), whereas WF and Lewis rat spleen cells and a rat pituitary cell line (GH3) were not lysed by lymphoid cells from D or DP rats. The cytotoxic cells were identified as natural killer (NK) cells since NK-sensitive cells (G1-TC and YAC-1 cell lines) were lysed by D and DP spleen cells, YAC-1 cells competed for the lysis of RIN islet cells by D spleen cells, lysis of RIN cells was increased by using D spleen cells from the low density fraction (large lymphocytes/monocytes) of a Percoll density gradient, and incubation of D spleen cells with an antiserum to NK cells (anti-asialo GM1 serum) and complement decreased monoclonal antibody-defined subsets containing NK cells (W3/13+ OX19- and OX8+), and this was accompanied by similar decreases in cytotoxicity to YAC-1, RIN, and WF islet cells. These studies demonstrate that NK cell activity is increased in BB/W diabetic and DP rats, and that islet cells can serve as targets for these NK cells. The findings suggest that NK cells may participate in the islet-directed cellular cytotoxic response leading to beta cell destruction and diabetes.
D000818:Animals; D000911:Antibodies, Monoclonal; D001327:Autoimmune Diseases / Q000276:immunology; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D007111:Immunity, Cellular; D007515:Islets of Langerhans / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008214:Lymphocytes / Q000145:classification; D008264:Macrophages / Q000276:immunology; D051381:Rats; D011922:Rats, Mutant Strains; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal