Natural killer cells become tolerogenic after interaction with apoptotic cells

NK cells are effectors in innate immunity and also participate in immunoregulation through the release of TGF-beta1 and lysis of activated/autoreactive T cells. Apoptotic cells (AC) have been shown to induce tolerogenic properties in innate immune cells, including macrophages and dendritic cells, but not NK cells. In this study, we demonstrated that after interaction with AC, NK cells released TGF-beta1, which in turn suppressed the production of IFN-gamma by NK cells upon IL-12 and IgG activation. We further identified phosphatidylserine as a potential target on AC for the NK cells, as phosphatidylserine could stimulate NK cells to release TGF-beta1, which in turn suppressed CD4(+) T-cell proliferation and activation. Moreover, AC-treated NK cells displayed cytotoxicity against autologous-activated CD4(+) T cells by upregulating NKp46. This lysis occurred in part through the NKp46-vimentin pathway, as activated CD4(+) T cells expressed vimentin on the cell surface and blocking of vimentin or NKp46, but not other NK-cell receptors, significantly suppressed the NK-cell cytotoxicity. We report here a novel interaction between NK cells and AC, resulting in the tolerogenic properties of NK cells required for immune contraction.