Expression of the NKG2D ligand UL16 binding protein‐1 (ULBP‐1) on dendritic cells

Abstract

Innate and adaptive immunity have not evolved separately. In this regard, the NKG2D molecule first identified on NK cells and classified as an activating NK cell receptor is also an important receptor for CD8 + T cells. Functional analyses of human NKG2D and its ligands, i.e. UL16 binding proteins (ULBP) and MHC class I chain-related (MIC), have so far focused on immune cell-target cell situations because of the expression of NKG2D ligands on infected, stressed or transformed cells. Here, however, we address a possible function of NKG2D/ULBP-1 during the initiation of T cell responses. ULBP-1 can be detected on mature dendritic cells both in situ in the T cell areas of lymph nodes as well as in vitro after artificial maturation. FCM analysis further demonstrated that although NKG2D is expressed to some degree on all analyzed T cell subsets from peripheral blood, in vitro stimulation of T cells results in up-regulation of NKG2D on proliferating T cells. Using the sentinel lymph nodes of primary melanoma as a model for induction of defined T cell responses in vivo, we were able to demonstrate the expression of NKG2D on melanoma-associated antigen-specific T cells. Thus, our results suggest a role for NGK2D-ULBP-1 in the induction or reactivation of T cell responses.

Dynamic Shift from CD85j/ILT-2 to NKG2D NK Receptor Expression Pattern on Human Decidual NK during the First Trimester of Pregnancy

“…We observed that ULBP-1 is the only NKG2D ligand expressed at the surface of dAPC and dLT cells. The ULBP-1 expression on decidual immune cells might be related to the cell maturation status [37], [38] and cytokines microenvironment [39] as it has been previously described on peripheral antigen presenting cells. Other studies have shown that the ligands of NKp44 are expressed by trophoblasts [23].…”

NKG2D ligands: key targets of the immune response

“…This induces NK cell-mediated cytotoxicity, which could allow the elimination of overstimulated macrophages and it might therefore serve to control the innate immune response [46]. NKG2DLs are also upregulated on dendritic cells by Toll-like receptor (TLR) ligand stimulation, and they might participate in the activation of T cells and NK cells [47,48]. Interestingly, T cell activation in vitro also upregulates NKG2DL expression, which could open up the adaptive immune response to control by NK cells [49][50][51].…”

NKG2D and DNAM-1 activating receptors and their ligands in NK-T cell interactions: role in the NK cell-mediated negative regulation of T cell responses

“…NKG2D ligands (NKG2DLs) are mainly induced on the surface of transformed, infected or otherwise “stressed” cells, while the expression on healthy cells is low. However, increasing evidences show that NKG2DLs can be constitutively expressed or induced on normal hematopoietic cells including bone marrow cells (Nowbakht et al, 2005; Poggi et al, 2005; Spaggiari et al, 2006), mature DCs (Jinushi et al, 2003a,b; Andoniou et al, 2005; Schrama et al, 2006; Galazka et al, 2007; Qiao et al, 2008), monocytes and macrophages (Hamerman et al, 2004; Nowbakht et al, 2005; Nedvetzki et al, 2007; Kloss et al, 2008; Schulz et al, 2010), B cells (Nowbakht et al, 2005), and T cells. In general, NKG2DLs are not expressed by resting T lymphocytes, but their expression can be induced by different stimuli ( Table 1 ).…”

“…Thus, the receptor/ligand interactions triggering a perforin-mediated cytotoxicity play a key role in controlling T cell responses, and NKG2D might be part of the picture, since it plays a major role in NK cell lysis of autologous activated T cells (Rabinovich et al, 2003; Cerboni et al, 2007a; Nielsen et al, 2012). Moreover, NK cells can lyse autologous DCs, that under certain circumstances – including EAE – express NKG2DLs (Jinushi et al, 2003a,b; Andoniou et al, 2005; Schrama et al, 2006; Galazka et al, 2007; Qiao et al, 2008). These data, together with NKG2DL expression also on activated macrophages and monocytes, bone marrow cells and microglia (Lünemann et al, 2008), indicate that this receptor/ligand pair might play a more general immunoregulatory role besides killing autoreactive T cells, e.g., by eliminating macrophages and other antigen-presenting cells or their precursors under inflammatory conditions, as a feedback mechanism to silence uncontrolled antigen-specific immune responses.…”