Interleukin 2 activates BB/W diabetic rat lymphoid cells cytotoxic to islet cells.
We compared the cytotoxic effects to islet cells of lymphoid cells from diabetic and diabetes-resistant (DR) BioBreeding/Worcester (BB/W) rats with a 51Cr-release assay to detect lysis of normal rat islet cells. Splenic lymphoid cells from diabetic rats were more cytotoxic to islet cells (11.3 +/- 3.8%) than were lymphoid cells from DR rats (4.0 +/- 2.6%). This difference was amplified by incubating the lymphoid cells for 20 h with 5 micrograms/ml concanavalin A (ConA); islet cell lysis was 39.3 +/- 4.5% by ConA-activated diabetic cells and 9.6 +/- 2.7% by ConA-activated DR cells. The cytotoxic lymphoid cells were identified as natural killer (NK) cells, because treatment of diabetic lymphoid cells with anti-asialo GM1 serum and complement selectively removed a monoclonal antibody-defined subset of NK cells (OX8 +), and the NK-depleted lymphoid cells were not cytotoxic to either islet or NK-sensitive YAC-1 cells, even after culture with ConA. Of several lymphokine products of ConA-stimulated lymphoid cells, interleukin 2 (IL-2), but not interleukin 1 or interferon-gamma, significantly activated splenic lymphoid cells cytotoxic to islet cells, and the lymphoid cells from diabetic rats were more sensitive to IL-2 (3 U/ml) than were the cells from DR rats (30 U/ml). This study reveals the presence of ConA- and IL-2-responsive islet cytotoxic NK cells in the diabetic BB/W rat and suggests that IL-2 activation of NK cells may contribute to islet beta-cell destruction and diabetes in this animal.
Pukel
C
C
Department of Medicine, University of Miami School of Medicine, FL 33101.
Baquerizo
H
H
Rabinovitch
A
A
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology; D007700:Kinetics; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*
D007375:Interleukin-1; D007376:Interleukin-2; D003208:Concanavalin A