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Diabetes, Vol 36, Issue 11 1217-1222, Copyright © 1987 by American Diabetes Association


ARTICLES

Interleukin 2 activates BB/W diabetic rat lymphoid cells cytotoxic to islet cells

C Pukel, H Baquerizo and A Rabinovitch
Department of Medicine, University of Miami School of Medicine, FL 33101.

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.
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T. Stewart, B Hultgren, X Huang, S Pitts-Meek, J Hully, and N. MacLachlan
Induction of type I diabetes by interferon-alpha in transgenic mice
Science, June 25, 1993; 260(5116): 1942 - 1946.
[Abstract] [PDF]




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Copyright © 1987 by the American Diabetes Association.