Regulation of immune responses by CD1d-restricted natural killer T cells

Natural killer T (NKT) cells are a unique subset of T lymphocytes that share receptor structures and properties with conventional T lymphocytes and natural killer (NK) cells. NKT cells are specific for glycolipid antigens such as the marine sponge-derived agent α-galactosylceramide (α-GalCer) presented by the major histocompatibility complex (MHC) class I-like molcule CD1d. My laboratory has evaluated the function of NKT cells by generating and analyzing CD1d-deficient mice. These studies showed that CD1d expression is required for NKT cell development, but not absolutely necessary for the generation of polarized T helper (Th) cell responses. Further, we have studied the in vivo response of NKT cells toα-GalCer stimulation and the capacity of α-GalCer to modulate innate and adaptive immune responses. Our results revealed that, quickly following administration of α-GalCer, NKT cells expand and produce cytokines, trans-activate a variety of innate and adaptive immune cells, and promote Th2 responses that are capable of suppressing Th1-dominant autoimmunity. Our findings indicate that NKT cells play a regulatory role in the immune response and that specific activation of these cells may be exploited for therapeutic purposes.     

Notch1 expression on T cells is not required for CD4+ T helper differentiation

Notch1 proteins are involved in binary cell fate decisions. To determine the role of Notch1 in the differentiation of CD4(+) Th1 versus Th2 cells, we have compared T helper polarization in vitro in naive CD4(+) T cells isolated from mice in which the N1 gene is specifically inactivated in all mature T cells. Following activation, Notch1-deficient CD4(+) T cells transcribed and secreted IFN-gamma under Th1 conditions and IL-4 under Th2 conditions at levels similar to that of control CD4(+) T cells. These results show that Notch1 is dispensable for the development of Th1 and Th2 phenotypes in vitro. The requirement for Notch1 in Th1 differentiation in vivo was analyzed following inoculation of Leishmania major in mice with a T cell-specific inactivation of the Notch1 gene. Following infection, these mice controlled parasite growth at the site of infection and healed their lesions. The mice developed a protective Th1 immune response characterized by high levels of IFN-gamma mRNA and protein and low levels of IL-4 mRNA with no IL-4 protein in their lymph node cells. Taken together, these results indicate that Notch1 is not critically involved in CD4(+) T helper 1 differentiation and in resolution of lesions following infection with L. major.     

Structures et propriétés diélectriques des poly(α-acétoxystyréne)s parasubstitués

The relations between structure and isothermal, dielectric properties of poly(α-acetoxystyrene)s substituted in para position by ? OCOCH₃ ( 1a ), ? OCOCH₂CH₃ ( 1b ), ? OCOCH₂CH₂CH₃ ( 1c ), ? OCOC₆H₅ ( 1d ), ? OCOCH₂CH₂Cl ( 1f ) and ? OCOOCH₃ ( 1g ) were studied. The dielectric constants, at 10⁵ Hz and 20 ± 2°C, were found to be: 3,79 ( 1a ), 3,36 ( 1b ), 3,18 ( 1c ), 3,51 ( 1d ), 3,36 ( 1e ), 3,65 ( 1f ) and 3,07 ( 1g ). The polymers 1a – 1g do not show any α- or β-transition. Increasing bulkiness of the para substituent gives rise to a decreasing dielectric constant due to an increase of the degree of syndiotacticity, as determined from ¹H and ¹³C NMR spectra.     

ARCHITECT® urine-neutrophil gelatinase-associated lipocalin (u-NGAL) assay as new prognostic marker for clear cell Renal Cell Carcinoma (ccRCC) (preliminary results)

International Urology and Nephrology - Biomarkers for the diagnosis and monitoring treatment response of kidney cancer are urgently needed. Neutrophil gelatinase-associated lipocalin (NGAL) is a...     

Urgent desensitization in patients bridged to heart transplantation under extracorporeal membrane oxygenation support: A preliminary experience

Antihuman leukocyte antigen (HLA) antibodies restrict the access to cardiac allografts. Desensitization therapy is a major challenge in patients with cardiogenic shock waiting for urgent heart transplantation (HT). We retrospectively reviewed six patients (mean age of 37.5 years [16–70]) who underwent plasmapheresis (PP) under extracorporeal membrane oxygenation (ECMO) before transplant between January 2017 and September 2018. The average duration of follow‐up was 25 months [20–32]. Mean fluorescence intensity (MFI) of HLA‐specific antibodies was reported as follows: score 4 for MFI < 1000, score 6 for 1000 < MFI < 3000 and score 8 for MFI > 3000. The mean duration of ECMO support was 29 days [1–74] and 6.8 [1–29] PP sessions were performed per patient before transplant. The mean number of HLA‐specific antibodies before HT was 9.6 for score 6 [4–13] and 5.8 for score 8 [1–12]. Four patients had major complications after transplantation (2 hemorrhagic shocks, 5 infectious events). Mean MFI reduction rate was 94% [79–100] for Class I and 44.2% for Class II [0–83]. Hospital survival was 100%, and early antibody‐mediated rejection was diagnosed in one patient at 7 days after HT. Plasmapheresis under ECMO support was associated with favorable early outcomes in highly sensitized candidates for urgent heart transplantation.     

Determinants of biosecurity practices in French duck farms after a H5N8 Highly Pathogenic Avian Influenza epidemic: The effect of farmer knowledge,attitudes and personality traits

Biosecurity is crucial for infectious disease prevention, more importantly in the absence of vaccination. The need for improving the implementation of biosecurity practices was highlighted in French duck farms following the 2016–2017 H5N8 Highly Pathogenic Avian Influenza (HPAI) epidemic. Farmers have multiple reasons for not implementing biosecurity practices: external (time, money) and internal (socio‐psychological). The purpose of this study was to determine how sets of socio‐psychological factors (i.e. knowledge on biosecurity and avian influenza transmission, attitudes, personality traits, social background) affect the adoption of on‐farm biosecurity practices. Biosecurity practices and socio‐psychological determinants were assessed during 127 duck farm visits, in South West France, using both questionnaires and on‐farm observations. Factorial analysis of mixed data (FAMD) and hierarchical clustering analysis (HCA) identified three groups of farmers with different socio‐psychological profiles: the first group was characterized by minimal knowledge, negative attitudes towards biosecurity, little social pressure and a low level of conscientiousness. The second group was characterized by more extensive experience in poultry production, higher stress and social pressure. The third group was characterized by less experience in poultry production, better knowledge and positive attitudes towards biosecurity, increased self‐confidence and orientation towards action. The first group had a significantly lower adoption of biosecurity measures than the two other groups. A better understanding of the factors involved in farmers' decision‐making could improve the efficiency of interventions aiming at improving and maintaining the level of on‐farm biosecurity in the duck industry.