Coengagement of CD16 and CD94 Receptors Mediates Secretion of Chemokines and Induces Apoptotic Death of Naive Natural Killer Cells

Abstract

Down-modulation of CD16 (FcgRIII) receptors and loss of natural killer (NK) cell function have been observed in oral cancer patients. However, neither the mechanisms nor the significance of the decrease in CD16 receptors have been fully understood. The cytotoxic activity and survival of NK cells are negatively regulated by antibodies directed against CD16 surface receptor. The addition of anti-CD94 antibody in combination with either F(abV ) 2 fragment or intact anti-CD16 antibody to NK cells resulted in significant inhibition of NK cell cytotoxic function and induction of apoptosis in resting human peripheral blood NK cells. Addition of interleukin-2 to anti-CD16 and/or anti-CD94 antibody-treated NK cells significantly inhibited apoptosis and increased the function of NK cells. There was a significant increase in tumor necrosis factor-a (TNF-a) but not IFN-g secretion in NK cells treated either with anti-CD16 antibody alone or in combination with anti-CD94 antibodies. Consequently, the addition of anti-TNF-a antibody partially inhibited apoptosis of NK cells mediated by the combination of anti-CD94 and anti-CD16 antibodies. Increase in apoptotic death of NK cells also correlated with an increase in type 2 inflammatory cytokines and in the induction of chemokines. Thus, we conclude that binding of antibodies to CD16 and CD94 NK cell receptors induces death of the NK cells and signals for the release of chemokines.

N-acetylcysteine protects dental pulp stromal cells from HEMA-induced apoptosis by inducing differentiation of the cells

“…Thus, one of the important functions of immune inflammatory cells in pulp is their enhancing effect on differentiation of DPSCs to withstand distinct environmental insults. In this regard most of the inflammatory cytokines induced in the cocultures of naïve immune effectors with DPSCs or keratinocytes such as IL-6, IL-1β and TNF-α have all inducing effect on NFκB activation and this may in part be responsible for the increased survival of DPSCs and keratinocytes (data not shown) [26].…”

Natural killer cells as effectors of selection and differentiation of stem cells: Role in resolution of inflammation

“…Indeed, blocking NF-B in oral tumors was found to increase their levels of CD44 surface receptor expression, one hallmark of stem cells the NK cells (Jewett et al, 2003(Jewett et al, , 2006a. Similarly, inhibition of NF-B by Sulindac increased the functional activation of NK cells and enhanced anti-tumor cytotoxic activity (Jewett et al, 2003(Jewett et al, , 2006b).…”

“…Addition of antibodies to CD56 or LFA-1 did not cause any decrease in NK cell cytotoxicity, demonstrating the specificity of anti-CD16 monoclonal antibody (mAb) signaling in mediating inhibition of NK cell cytotoxicity (Jewett & Bonavida, 2000). Thus, we coined the term 'split anergy' for responses mediated by NK cells after their interaction with sensitive target cells or after the triggering of CD16 receptors by the antibody in combination with IL-2 treatment (Jewett & Bonavida, 1995Jewett et al, 1997;Jewett et al, 2006aJewett et al, , 2008 (Bonavida et al, 1993;Jewett & Bonavida, 1994.…”

“…Furthermore, NK cells exhibited a CD16 À CD56 dim/À CD69 + phenotype after treatment with the combination of IL-2 and anti-CD16 mAb (Jewett & Bonavida, 2000;Jewett et al, 1997Jewett et al, , 2006aJewett et al, , 2008. Loss of cytotoxicity in NK cells was significantly exacerbated when NK cells were either treated with F(ab)' 2 fragment of anti-CD16 mAb with IL-2 or treated with a combination of MHC Class I and anti-CD16 mAb in combination with IL-2, while the same treatments resulted in an increased secretion of cytokines (Jewett & Bonavida, 2000;Jewett et al, 2008).…”

Impaired T lymphocyte function increases tumorigenicity and decreases tumor latency in a mouse model of head and neck cancer

“…Later stages of tumor development may include cells which are less immunogenic. Natural killer and cytotoxic T lymphocytes which have crucial effector functions in immune defense against tumor cells are inactivated in HNSCC (12,13). Regression of tumor grafts is characterized by NK and cytotoxic T lymphocyte attack, and patients with metastatic HNSCC have low NK and cytotoxic T lymphocyte activity (14,15).…”