Abundant cytomegalovirus (CMV) reactive clonotypes in the CD8(+) T cell receptor alpha repertoire following allogeneic transplantation.

Allogeneic stem cell transplantation is potentially curative, but associated with post-transplantation complications, including cytomegalovirus (CMV) infections. An effective immune response requires T cells recognizing CMV epitopes via their T cell receptors (TCRs). Little is known about the TCR repertoire, in particular the TCR-α repertoire and its clinical relevance in patients following stem cell transplantation. Using next-generation sequencing we examined the TCR-α repertoire of CD8(+) T cells and CMV-specific CD8(+) T cells in four patients. Additionally, we performed single-cell TCR-αß sequencing of CMV-specific CD8(+) T cells. The TCR-α composition of human leucocyte antigen (HLA)-A*0201 CMVpp65- and CMVIE -specific T cells was oligoclonal and defined by few dominant clonotypes. Frequencies of single clonotypes reached up to 11% of all CD8(+) T cells and half of the total CD8(+) T cell repertoire was dominated by few CMV-reactive clonotypes. Some TCR-α clonotypes were shared between patients. Gene expression of the circulating CMV-specific CD8(+) T cells was consistent with chronically activated effector memory T cells. The CD8(+) T cell response to CMV reactivation resulted in an expansion of a few TCR-α clonotypes to dominate the CD8(+) repertoires. These results warrant further larger studies to define the ability of oligoclonally expanded T cell clones to achieve an effective anti-viral T cell response in this setting.

[Evidence-based therapy of depression: S3 guidelines on unipolar depression]. / Evidenzbasierte Therapie der Depression: Die S3-Leitlinie unipolare Depression.

Unipolar depressive disorders are among the most frequent reasons for utilizing the health care system. Although efficacious treatments are available and further advances have recently been made there is still a need for improving diagnostic and therapeutic procedures. Alignment of treatment on evidence-based treatment guidelines establishes an essential mainstay. The new S3 and National Health Care guidelines on unipolar depression, the compilation of which was coordinated by the German Society of Psychiatry, Psychotherapy and Neurology (DGPPN) and which were approved by 29 scientific and professional associations, is the ambitious effort to present state of the art evidence and clinical consensus for the treatment of depression. For pharmacotherapy of depression differentiated recommendations can be given, also separate from and in addition to psychotherapy.

[Affective disorders. The significance of psychotherapeutic approaches]. / Depressive Störungen. Stellenwert psychotherapeutischer Verfahren.

The use of psychotherapeutic strategies is essential in the treatment of affective disorders. Psychotherapy proved to be at least equivalent to antidepressant medication in the treatment of mild to moderate depression. In severe cases, the combination of both treatments is considered by guidelines to be the standard treatment. Psychotherapeutic approaches show a longer latency than antidepressants; however, the effects are longer lasting. Regarding the effectiveness of pharmacotherapy sobering results have been published recently. Therefore, the further development of psychotherapy deserves special attention. Cognitive behavioral therapy and interpersonal therapy provide the highest evidence. The empirical basis for psychodynamic psychotherapies is still limited. In the treatment of chronic depression a new approach--cognitive behavioral analysis system of psychotherapy--is gaining importance. There is a trend towards an increasing specification of psychotherapy for distinct subgroups of depressed patients. Challenges for the future include increasing treatment efficacy, investigating mechanisms of efficacy and predictors for a differential indication, and making effective approaches generally available to all patients.

[Development of national guidelines for depression]. / Entwicklung der S3- und Nationalen Versorgungs-Leitlinie Depression.

Depressive disorders rank among the most frequent causes of consultation and diseases in health care. Although they are treatable, there is further need to optimize diagnostics and therapy, despite sizable progress in recent years. The implementation of evidence- and consensus-based guidelines is an appropriate measure to improve care for depressive patients. An evidence-based guideline for depression is currently being developed for Germany. In order to ensure its acceptance and a wide dissemination, this guideline will be adopted in consensus by all relevant health care providers in this field. According to this, it is a future challenge to anchor guideline-based diagnostics and treatment in routine care.

[Innovative care models for treating depression]. / Neue Versorgungsmodelle in der Depressionsbehandlung.

Depressive disorders rank among the widespread diseases, and their relevance for the health care system is steadily increasing. Even though depressive disorders can generally be treated well, there is a further need to improve the care for depressive patients with regard to diagnostics, therapy, and cooperation of care sectors. Innovative and integrative models of care such as case management, disease management programs, and integrated care models are currently being discussed. They are expected to be useful in overcoming boundaries in the current care system and amending the course of disease and of patients' quality of life. Furthermore, changes in utilization of the health system are anticipated, leading to a diminishment of deficient care, undersupply and oversupply, and chronification. However, evidence is lacking to demonstrate the usefulness of these models of care in Germany now.