Control of Immune Response to Allogeneic Embryonic Stem Cells by CD3 Antibody-Mediated Operational Tolerance Induction.

Implantation of embryonic stem cells (ESCs) and their differentiated derivatives into allogeneic hosts triggers an immune response that represents a hurdle to clinical application. We established in autoimmunity and in transplantation that CD3 antibody therapy induces a state of immune tolerance. Promising results have been obtained with CD3 antibodies in the clinic. In this study, we tested whether this strategy can prolong the survival of undifferentiated ESCs and their differentiated derivatives in histoincompatible hosts. Recipients of either mouse ESC-derived embryoid bodies (EBs) or cardiac progenitors received a single short tolerogenic regimen of CD3 antibody. In immunocompetent mice, allogeneic EBs and cardiac progenitors were rejected within 20-25 days. Recipients treated with CD3 antibody showed long-term survival of implanted cardiac progenitors or EBs. In due course, EBs became teratomas, the growth of which was self-limited. Regulatory CD4(+)FoxP3(+) T cells and signaling through the PD1/PDL1 pathway played key roles in the CD3 antibody therapeutic effect. Gene profiling emphasized the importance of TGF-ß and the inhibitory T cell coreceptor Tim3 to the observed effect. These results demonstrate that CD3 antibody administered alone promotes prolonged survival of allogeneic ESC derivatives and thus could prove useful for enhancing cell engraftment in the absence of chronic immunosuppression.

["Mental Health in the General Population: images and realities (MHGP)": methodology of the study]. / "Santé Mentale en Population Générale : Images et Réalités (Smpg)" : Présentation de La méthodologie d'enquête.

INTRODUCTION: Mental Health is a Public Health issue, however, access to relevant treatment often does not meet the population needs. Patients, their relatives, as well as Mental Health professionals are still victims of a high stigmatization process. Whatever the countries and the cultural settings, public beliefs and attitudes towards mental illness (insanity) and mentally ills (insane people) play a major role in the ranking of priorities given to Mental Health national prevention and care policies. This paper presents the methodology of the research-action entitled "Mental Health in General Population: images and realities (MHGP)" carried out by the World Health Organisation Collaborative Centre (Lille, France) and the Direction of research, studies, assessment and statistics (Drees) of the French Ministry of Health, in a sample of 36 000 French subjects over 18 years old, between 1999 and 2003. OBJECTIVES: The MHGP Survey is an international multisite study aimed at: Describing, in the general population, the representations attached to insanity, mental illness and depression, and the related care; Assessing the prevalence of major psychiatric disorders in the general population; Rising awareness about Mental Health issues among various social groups: social workers, local elected, care professionals, by including them in the research-action procedure; Promoting the development of Community Psychiatry, following WHO main Guidelines. METHODS: About 900 individuals were recruited in 47 centres in metropolitan France between 1999 and 2003 according to the following criteria: i) informed consent to take part in the study, ii) age over 18 yrs, iii) not residing in a care institution and not homeless. Subjects were selected by quota sampling stratified by age, gender, educational and occupational level with the general population of the general population of the centre as sampling frame. The quotas were defined on the basis of the 1999 national population census. The data was collected by 1700 nursing students using a 50-item structured questionnaire administered in face-to-face interviews; mean length 40 minutes. The interviewers received a special 3-day training course. The assessment included a specially developed questionnaire enabling description of representations of insane, mentally ill and depressed individuals; the Mini International Neuro-psychiatric Interview (Sheehan and Lecrubier); a specific questionnaire on care consumption in case of positive MINI diagnosis and a sociodemographic questionnaire. In each centre, a team of supervisors (psychiatric staff) coordinated the interviews and the data collection; the local elected and the social and care networks were given information about the research and the results. The results of the local study were systematically presented to the general population, the local elected and the social and care professionals. Prevalence rates of mental disorders are very similar to those observed in other studies. Results on social representations and public beliefs in general population can compare with the international data available. MHGP research-action remains the first study of this scale on the topic of Mental Health in France, combining representations and prevalences description. It allowed the development of anti-stigma actions at a national and local level.

Prevalence, characteristics and comorbidities of anxiety disorders in France: results from the "Mental Health in General Population" survey (MHGP).

PURPOSE: Only a few European countries have carried out large, community-based, national surveys about psychiatric morbidity. Here is presented the first national French survey, aiming to estimate the prevalence of anxiety disorders and associated comorbidities according to sociodemographic characteristics. MATERIALS AND METHODS: The Mental Health in General Population (MHGP) database is derived from a representative national survey of the French adult population (n=36,105), conducted between 1999 and 2003. Data collection was done using an anonymous face-to-face interview. The presence of anxiety disorders (generalized anxiety disorder, panic disorder, agoraphobia, social phobia and post-traumatic stress disorder) was assessed using the Mini International Neuropsychiatric Interview. RESULTS: The overall prevalence of anxiety disorders was estimated to be 21.6%, generalized anxiety disorder being the most prevalent one (12.8%). Women, young people, and people earning low income were identified as the more at risk. Major depressive episode, alcohol abuse and drug addiction frequently co-occur with anxiety disorders (28.3, 4.4 and 2.8% respectively). CONCLUSION: The MHGP study showed that anxiety disorders are highly prevalent in France with a high frequency of comorbidities. Our results highlight the need for considering anxiety disorders as a public health priority in France as well as in other European countries.

Isolated spleen agenesis: a rare cause of thrombocytosis mimicking essential thrombocythemia.

Thrombocytosis is a common feature of myeloproliferative disorders but may also result from various conditions including chronic iron deficiency, hemorrhage, chronic inflammation and splenectomy. We report two cases of secondary thrombocytosis caused by isolated and congenital asplenia, mimicking essential thrombocythemia. These two adult cases of spleen agenesis were unexpected. We conclude that in thrombocytosis without clinical evidence of splenomegaly, attentive screening of blood in search of Howell-Jolly bodies and abdominal ultrasonography should always be performed not only to detect mild spleen enlargement but also to make sure of the presence of this organ.