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

Diabetes. 1987 Nov;36(11):1217-22. doi: 10.2337/diab.36.11.1217.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Concanavalin A / pharmacology
  • Cytotoxicity, Immunologic*
  • Diabetes Mellitus, Experimental / immunology*
  • Female
  • Interleukin-1 / pharmacology*
  • Interleukin-2 / pharmacology*
  • Islets of Langerhans / immunology*
  • Killer Cells, Natural / cytology
  • Kinetics
  • Phenotype
  • Rats
  • Rats, Inbred Strains
  • T-Lymphocytes / classification
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Interleukin-1
  • Interleukin-2
  • Concanavalin A