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 μg/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-γ, 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 β-cell destruction and diabetes in this animal.
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Original Contributions| November 01 1987
Interleukin 2 Activates BB/W Diabetic Rat Lymphoid Cells Cytotoxic to Islet Cells
Address correspondence and reprint requests to Alexander Rabinovitch, MD, Department of Medicine (R-134), University of Miami School of Medicine, P.O. Box 016960, Miami, FL 33101.
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Clifford Pukel, Hernan Baquerizo, Alexander Rabinovitch; Interleukin 2 Activates BB/W Diabetic Rat Lymphoid Cells Cytotoxic to Islet Cells. Diabetes 1 November 1987; 36 (11): 1217–1222. https://doi.org/10.2337/diab.36.11.1217
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