The mouse T-lymphocyte-activating molecule THAM is associated to ECTO-aminopeptidase activity

In the mouse there are three non-CD3/T-cell receptor T cell-activating molecules, Thy-1, Ly-6 antigens, and the CD28 homologue. Using a mitogenic rat monoclonal antibody, we identified a novel thymocyte-activating molecule (THAM). Here we review the main characteristics of this heterodimeric glycoprotein with respect to its expression on lymphoid and non-lymphoid cells, and its biochemical and T-cell-activating properties. THAM shares a number of structural features with surface peptidases of epithelial cell brush borders, and is in fact associated with a neutral aminopeptidase activity. The biologic significance of this observation is discussed in the context of recent data on the involvement of several ecto-enzymes in T-cell activation and differentiation.     

Lymphocyte transformation in patients with staged mycosis fungoides and Sézary syndrome.

Lymphocyte transformation was studied in patients with mycosis fungoides and the Sézary syndrome with particular reference to the stage of disease. Phytohemagglutinin-induced lymphocyte blastogenesis was normal in stage II, became depressed in stage III and was greatly reduced in stage IV disease. Similar abnormalities were found in patients with the Sézary syndrome once the proportion of abnormal cells in the peripheral blood exceeded 10%. It is concluded that stag III mycosis fungoides is probably a critical period in determining dissemination of the disease.     

Immunoregulatory functions of paf-acether. II. Decrease of CD2 and CD3 antigen expression

Paf-acether (platelet-activating factor) is a phospholipid initially described as a potent platelet-aggregating compound. It is produced by numerous cell types and is now considered as an important mediator of cell-cell interactions. The effect of paf-acether on the expression of CD2 and CD3, two human T cell surface glycoproteins, was investigated by indirect immunofluorescence and flow cytometry. Paf-acether partially down-regulated, in a time- and dose-dependent manner, CD2 and CD3 but not HLA class I antigen expression on peripheral human T cells and Jurkat cells. Lysophosphatidylcholine, a phospholipid closely related to paf-acether, had no detectable modulatory effect on CD2 and CD3 expression. In addition to CD2/CD3 modulation, paf-acether markedly inhibited T cell proliferative response not only to phytohemagglutinin or concanavalin A but also to anti-CD3 or a stimulatory combination of anti-CD2 monoclonal antibodies. These data demonstrate for the first time that lipid mediators such as paf-acether might be involved in the regulation of the expression of cell surface glycoproteins that are essential in the execution of T cell function.     

Coordination of activating and inhibitory signals in natural killer cells

NK cells are equipped with multiple activating and inhibitory cell surface receptors whose engagement regulate NK cell effector function (i.e. cytotoxicity as well as chemokine and cytokine production). Several components (adaptors, effector molecules) that participate to NK cell signalling pathways have been described. Yet, the spatio-temporal organisation of these pathways is still poorly understood. In addition, the mechanisms that integrate several simultaneous input signals in NK cells remain to be elucidated.     

Impact of β2 integrin deficiency on mouse natural killer cell development and function

Natural killer (NK) cells are innate immune cells that express members of the leukocyte β2 integrin family in humans and mice. These CD11/CD18 heterodimers play critical roles in leukocyte trafficking, immune synapse formation, and costimulation. The cell-surface expression of one of these integrins, CD11b/CD18, is also recognized as a major marker of mouse NK-cell maturation, but its function on NK cells has been largely ignored. Using N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated a mouse carrying an A → T transverse mutation in the Itgb2 gene, resulting in a mutation that prevented the cell-surface expression of CD18 and its associated CD11a, CD11b, and CD11c proteins. We show that β2 integrin-deficient NK cells have a hyporesponsive phenotype in vitro, and present an alteration of their in vivo developmental program characterized by a selective accumulation of c-kit(+) cells. NK-cell missing-self recognition was partially altered in vivo, whereas the early immune response to mouse cytomegalovirus (MCMV) infection occurred normally in CD18-deficient mice. Therefore, β2 integrins are required for optimal NK-cell maturation, but this deficiency is partial and can be bypassed during MCMV infection, highlighting the robustness of antiviral protective responses.     

MR urography in children. Part 1: how we do the F0 technique

MR urography (MRU) has been widely accepted as a substitute to intravenous urography for investigating children with a dilated urinary tract after preliminary assessment by US and voiding cystourethrography. Hydronephrosis is by far the main indication for MRU because upper tract dilatation is a frequent condition in infants and children. Recent advances in technology have allowed MR to go beyond morphology and to assess renal function parameters such as split renal function and drainage. In this article we report our routine practice of the F0 MRU technique. The main advantages of our protocol are no requirement for general anaesthesia, no bladder catheterization, use of low-dose gadolinium-based contrast agent (0.05–0.1 mmol/kg) and total acquisition time of 30 min or less.     

Genetic and antibody-mediated reprogramming of natural killer cell missing-self recognition in vivo

Natural killer (NK) cells are lymphocytes of the innate immune system able to recognize and kill tumors lacking self-MHC class I molecules. This “missing-self” recognition is mediated by the lack of engagement of MHC class I-specific inhibitory NK cell receptors that include the killer cell Ig-like receptors (KIR) in humans and Ly49 molecules in mice. A promising immunotherapeutic strategy against MHC class I⁺ cancer cells is to block NK cell inhibitory receptors using monoclonal antibodies (mAb). However, interactions between MHC class I molecules and their inhibitory receptors are also required for the acquisition of NK cell functional competence, a process referred as to “education.” In addition, inhibitory receptors are involved in self-tolerance on educated NK cells. Here, we developed a preclinical mouse model in which all NK cells are educated by a single transgenic inhibitory receptor, human KIR2DL3, through the engagement with its HLA-Cw3 ligand. This approach revealed that NK cells could be reprogrammed to control the development of mouse syngenic tumors in vivo. Moreover, in vivo anti-KIR mAb treatment induced the killing of HLA⁺ target cells without breaking self-tolerance. Finally, the long-term infusion of anti-KIR mAb neither abolished NK cell education nor tumor cell recognition. Therefore, these results strongly support the use of inhibitory receptor blockade in cancer patients.