The interaction between CD300a and phosphatidylserine inhibits tumor cell killing by NK cells

The activity of NK cells is controlled by inhibitory and activating receptors. The inhibitory receptors interact mostly with MHC class I proteins, however, inhibitory receptors such as CD300a, which bind to non‐MHC class I ligands, also exist. Recently, it was discovered that phosphatidylserine (PS) is a ligand for CD300a and that the interaction between PS expressed on apoptotic cells and CD300a inhibits the uptake of apoptotic cells by phagocytic cells. Whether PS can inhibit NK‐cell activity through CD300a is unknown. Here, we have generated specific antibodies directed against CD300a and we used these mAbs to demonstrate that various NK‐cell clones express different levels of CD300a. We further demonstrated that both CD300a and its highly homologous molecule CD300c bind to the tumor cells equally well and that they recognize PS and additional unknown ligand(s) expressed by tumor cells. Finally, we showed that blocking the PS–CD300a interaction resulted in increased NK‐cell killing of tumor cells. Collectively, we demonstrate a new tumor immune evasion mechanism that is mediated through the interaction between PS and CD300a and we suggest that CD300c, similarly to CD300a, also interacts with PS

Inhibitory NK Receptor Recognition of HLA-G: Regulation by Contact Residues and by Cell Specific Expression at the Fetal-Maternal Interface

The non-classical HLA-G protein is distinguished from the classical MHC class I molecules by its expression pattern, low polymorphism and its ability to form complexes on the cell surface. The special role of HLA-G in the maternal-fetal interface has been attributed to its ability to interact with specific receptors found on maternal immune cells. However this interaction is restricted to a limited number of receptors. In this study we elucidate the reason for this phenomenon by comparing the specific contact residues responsible for MHC-KIR interactions. This alignment revealed a marked difference between the HLA-G molecule and other MHC class I molecules. By mutating these residues to the equivalent classical MHC residues, the HLA-G molecule regained an ability of interacting with KIR inhibitory receptors found on NK cells derived either from peripheral blood or from the decidua. Functional NK killing assays further substantiated the binding results. Furthermore, double immunofluorescent staining of placental sections revealed that while the conformed form of HLA-G was expressed in all extravillous trophoblasts, the free heavy chain form of HLA-G was expressed in more distal cells of the column, the invasion front. Overall we suggest that HLA-G protein evolved to interact with only some of the NK inhibitory receptors thus allowing a control of inhibition, while permitting appropriate NK cell cytokine and growth factor production necessary for a viable maternal fetal interface

Effect of CMV and Aging on the Differential Expression of CD300a, CD161, T-bet, and Eomes on NK Cell Subsets

Natural killer cells are innate lymphoid cells involved in the defence against virus-infected cells and tumour cells. NK cell phenotype and function is affected with age and CMV latent infection. Aging affects the frequency and phenotype of NK cells and CMV infection also contributes to these alterations. Thus, a reduction of CD56bright NK cell subpopulation associated with age and an expansion of memory-like NK cells CD56dimCD57+NKG2C+ probably related to CMV-seropositivity have been described. NK cells express T-bet and Eomes transcription factors that are necessary for the development of NK cells. Here we analyse the effect of age and CMV-seropositivity on the expression of CD300a and CD161 inhibitory receptors and T-bet and Eomes transcription factors in NK cell subsets defined by the expression of CD56 and CD57. CD300a is expressed by the majority of NK cells. CD56bright NK cells express higher levels of CD300a than CD56dim NK cells. An increase in the expression of CD300a was associated with age whereas a decreased expression of CD161 in CD56dim NK cells was associated with CMV-seropositivity. In CD56dim NK cells an increased percentage of CD57+CD300a+ and a reduction in the percentage of CD161+CD300a+ cells were found to be associated with CMV-seropositivity. Regarding T-bet and Eomes transcription factors, CMV-seropositivity was associated with a decrease of T-bethi in CD56dimCD57+ NK cells from young individuals whereas Eomes expression was increased with CMV-seropositivity in both CD56bright and CD56dimCD57+/− (from middle-age and young individuals, respectively) and was decreased with ageing in all NK subsets from the three group of age. In conclusion, CMV infection and age induce significant changes in the expression of CD300a and CD161 in NK cell subsets defined by the expression of CD56 and CD57. T-bet and Eomes are differentially expressed on NK cell subsets and their expression is affected by CMV latent infection and ageing

Entretiens de Guillaume Le Gall avec Patrick Tosani, Thomas Billard et Philippe Lankry autour de la Cité Traëger (Paris)

Le Gall Guillaume, Tosani Patrick, Billard Thomas, Lankry Philippe. Entretiens de Guillaume Le Gall avec Patrick Tosani, Thomas Billard et Philippe Lankry autour de la Cité Traëger (Paris). In: Histoire de l'art, N°72, 2013. L’art de la façade. pp. 35-42

An Elderly Man with Atypical Multiple Evanescent White Dot Syndrome

A rare occurrence of an atypical case of multiple evanescent white dot syndrome (MEWDS) in a 75-year-old man without viral prodrome or white dots on fundus that presented with acute, severe left eye visual loss, which returned to baseline without treatment in several weeks. Multimodal imaging, including fluorescein angiography (FA), fundus autofluorescence (FAF), indocyanine green angiography (ICG), and optical coherence tomography (OCT) demonstrated classical presentation of MEWDS with wreath-like lesions and inflammatory foci in the retinal pigment epithelium that correlated among modalities. Possible underlying systemic disorders were ruled out through extended work up. To the best of our knowledge, this is the first report to show atypical MEWDS in an elderly man with classic changes on FA, FAF, ICG, and OCT