BACKGROUND In the early stages of human placentation, the decidua is invaded by fetal extravillous trophoblast (EVT) cells. Interactions between EVT cells and local decidual leukocytes are likely to contribute to immunological accommodation of the semi-allogeneic fetus. METHODS AND RESULTS Natural-killer group 2 member D (NKG2D) and 2B4 (CD244) are receptors ubiquitously expressed by the dist...

NKG2D is an activating receptor on T cells, which has been implicated in the pathogenesis of autoimmune diseases. T cells are critically involved in idiopathic inflammatory myopathies (IIM) and have been proposed as specific therapeutic targets. However, the mechanisms underlying T cell-mediated progressive muscle destruction in IIM remain to be elucidated. We here determined the involvement of...

Interleukin-2 (IL-2) has been shown to promote tumor-specific T-cell proliferation and differentiation but systemic administration of IL-2 results in significant toxicity. Therefore, a strategy that can specifically deliver IL-2 to the tumor location may alleviate concerns of toxicity. Because NKG2D ligands have been shown to be highly expressed in many cancer cells but not in healthy cells, we...

Monoclonal antibodies represent a promising approach to fight a variety of tumors, but their mode of action remains to be fully understood. NK cells can recognize Ab-coated targets, as well as stress ligands, on tumor cells. In this study, we investigated how NK cells integrate both kinds of activating signals. NK cell-mediated killing was maximal with the combined recognition of NKG2D ligands ...

Engineering T cells with chimeric antigen receptors (CARs) has emerged as a promising approach to adoptive T cell therapy for cancer. We have been studying CARs that employ the ligand-binding domain of the NKG2D receptor to target tumors. NKG2D ligand expression is increased on the surface of stressed cells, like tumor cells, making this family of ligands a target of interest for cancer immunot...

Expression of the stress-induced ligands MICA, MICB and ULBP 1-6 are up-regulated as a cellular response to DNA damage, excessive proliferation or viral infection; thereby, they enable recognition and annihilation by immune cells that express the powerful activating receptor NKG2D. This receptor is present not exclusively, but primarily on NK cells. Knowledge about the regulatory mechanisms con...

NK cells express an array of activating and inhibitory receptors, which facilitate the recognition and lysis of virally infected and transformed cells, but safeguard healthy cells from attack. NKG2D is an activating receptor expressed on the surface of NK cells that recognizes the ligands MICA/B and ULBP in human, which can be expressed on tumor cells or virus-infected cells. While NKG2D-mediat...

The NKG2D receptor stimulates natural killer cell and T cell responses upon engagement of ligands associated with malignancies and certain autoimmune diseases. However, conditions of persistent NKG2D ligand expression can lead to immunosuppression. In cancer patients, tumor expression and shedding of the MHC class I-related chain A (MICA) ligand of NKG2D drives proliferative expansions of NKG2D...

The activation NKG2D receptor has been shown to play an important role in the control of experimental tumor growth and metastases expressing ligands for NKG2D; however, a function for this recognition pathway in host protection from de novo tumorigenesis has never been demonstrated. We show that neutralization of NKG2D enhances the sensitivity of wild-type (WT) C57BL/6 and BALB/c mice to methyl...