An indirect role for NK cells in a CD4+ T-cell-dependent mouse model of type I diabetes

CD8(+) T cells kill pancreatic beta-cells in a cell-cell contact-dependent mechanism in the non-obese diabetic mouse. CD4(+) T lymphocytes are also able to kill pancreatic b-cells, but they do not directly contact beta-cells and may use another cell type as the actual cytotoxic cell. Natural killer (NK) cells could have this role but it is uncertain whether they are cytotoxic towards b-cells. Therefore, the requirement for NK cells in beta-cell destruction in the CD4-dependent T-cell antigen receptor transgenic NOD4.1 mice was examined. NK cells failed to kill b-cells in vitro, even in the absence of major histocompatibility complex class I. We observed only 9.7 +/- 1.1% of islet infiltrating NK cells from NOD4.1 mice expressing the degranulation marker CD107a. Diabetogenic CD4(+) T cells transferred disease to NODscid. IL2R gamma(-/-) mice lacking NK cells, indicating that NK cells do not contribute to beta-cell death in vitro or in vivo. However, depletion of NK cells reduced diabetes incidence in NOD4.1 mice, suggesting that NK cells may help to maintain the right environment for cytotoxicity of effector cells. Immunology and Cell Biology (2012) 90, 243-247; doi:10.1038/icb.2011.16; published online 8 March 2011