CD8+ T cells and NK cells from blister fluid of an EEM/SJS overlap highly express Fas ligand and Granulysin

INTRODUCTION Erythema exsudativum multiforme majus (EEMM) and Stevens-Johnson Syndrome (SJS) are severe cutaneous reaction patterns caused by infections or drug hypersensitivity. The mechanism by which widespread keratinocyte death is mediated by the immune system in EEMM/SJS are still to be elucidated. Here, we characterized the blister cells isolated from a patient with EEMM/SJS overlap and investigated its cause. METHODS Clinical classification of the cutaneous eruption was done according to the consensus definition of severe blistering skin reactions and histological analysis. Common infectious causes of EEMM were investigated using standard clinical techniques. T cell reactivity for potentially causative drugs was assessed by lymphocyte transformation tests (LTT). Lymphocytes isolated from blister fluid were analyzed for their expression of activation markers and cytotoxic molecules using flow cytometry. RESULTS The healthy 58 year-old woman suffered from mild respiratory tract infection and therefore started treatment with the secretolytic drug Ambroxol. One week later, she presented with large palmar and plantar blisters, painful mucosal erosions, and flat atypical target lesions and maculae on the trunc, thus showing the clinical picture of an EEMM/SJS overlap (Fig. 1). This diagnosis was supported by histology, where also eosinophils were found to infiltrate the upper dermis, thus pointing towards a cutaneous adverse drug reaction (cADR). Analysis of blister cells showed that they mainly consisted of CD8+ and CD4+ T cells and a smaller population of NK cells. Both the CD8+ T cells and the NK cells were highly activated and expressed Fas ligand and the cytotoxic molecule granulysin (Fig. 2). In addition, in comparison to NK cells from PBMC, NK cells in blister fluids strongly upregulated the expression of the skin-homing chemokine receptor CCR4 (Fig 4). Surprisingly, the LTT performed on PBMCs in the acute phase was positive for Ambroxol (SI=2.9) whereas a LTT from a healthy but exposed individual did not show unspecific proliferation. Laboratory tests for common infectious causes of EEMM were negative (HSV-1/-2, M. pneumoniae, Parvovirus B19). However, 6 weeks later, specific proliferation to Ambroxol could no longer be observed in the LTT (Fig 4.).

Plakoglobin-dependent disruption of the desmosomal plaque in pemphigus vulgaris

We recently reported that the pathogenesis of pemphigus vulgaris (PV), an autoimmune blistering skin disorder, is driven by the accumulation of c-Myc secondary to abrogation of plakoglobin (PG)-mediated transcriptional c-Myc suppression. PG knock-out mouse keratinocytes express high levels of c-Myc and resemble PVIgG-treated wild-type keratinocytes in most respects. However, they fail to accumulate nuclear c-Myc and loose intercellular adhesion in response to PVIgG-treatment like wild-type keratinocytes. This suggested that PG is also required for propagation of the PVIgG-induced events between augmented c-Myc expression and acantholysis. Here, we addressed this possibility by comparing PVIgG-induced changes in the desmosomal organization between wild-type and PG knock-out keratinocytes. We found that either bivalent PVIgG or monovalent PV-Fab (known to trigger blister formation in vivo) disrupt the linear organization of all major desmosomal components along cell borders in wild-type keratinocytes, simultaneously with a reduction in intercellular adhesive strength. In contrast, PV-Fab failed to affect PG knock-out keratinocytes while PVIgG cross-linked their desmosomal cadherins without significantly affecting desmoplakin. These results identify PG as a principle effector of the PVIgG-induced signals downstream of c-Myc that disrupt the desmosomal plaque at the plasma membrane.

Emotional contagion in team sports and its impact on individual performance – an experimental study

In sport psychology research about emotional contagion in sport teams has been scarce (Reicherts & Horn, 2008). Emotional contagion is a process leading to a specific emotional state in an individual caused by the perception of another individual’s emotional expression (Hatfield, Cacioppo & Rapson, 1994). Apitzsch (2009) described emotional contagion as one reason for collapsing sport teams. The present study examined the occurrence of emotional contagion in dyads during a basketball task and the impact of a socially induced emotional state on performance. An experiment with between-subjects design was conducted. Participants (N=81, ♀=38, M=21.33 years, SD=1.45) were randomly assigned to one of two experimental conditions, by joining a confederate to compose a same gender, ad hoc team. The team was instructed to perform a basketball task as quickly as possible. The between-factor of the experimental design was the confederate’s emotional expression (positive or negative valence). The within-factor was participants’ emotional state, measured pre- and post-experimentally using PANAS (Krohne, Egloff, Kohlmann & Tausch, 1996). The basketball task was video-taped and the number of frames participants needed to complete the task was used to determine the individual performance. The confederate’s emotional expression was appraised in a significantly different manner across both experimental conditions by participants and video raters (MC). Mixed between-within subjects ANOVAs were conducted to examine the impact of the two conditions on participants’ scores on the PANAS subscales across two time periods (pre- and post-experimental). No significant interaction effects but substantial main effects for time were found on both PANAS subscales. Both groups showed an increase in positive and a reduction in negative PANAS scores across these two time periods. Nevertheless, video raters assessment of the emotional states expressed by participants was significantly different between the positive (M=3.23, SD=0.45) and negative condition (M=2.39, SD=0.53; t=7.64, p<.001, eta squared=.43). An independent-samples t-test indicated no difference in performance between conditions. Furthermore, no significant correlation between the extent of positive or negative emotional contagion and the number of frames was observed. The basketball task lead to an improvement of the emotional state of participants, independently of the condition. Even though participants PANAS scores indicated a tendency to emotional contagion, it was not statistically significant. This could be explained by the low task duration of approximately three minutes. Moreover, the performance of participants was unaffected by the experimental condition or the extent of positive or negative emotional contagion. Apitzsch, E. (2009). A case study of a collapsing handball team. In S. Jern & J. Näslund (Eds.), Dynamics within and outside the lab. Proceedings from The 6th Nordic Conference on Group and Social Psychology, May 2008, Lund, pp. 35-52. Hatfield, E., Cacioppo, J. T. & Rapson, R. L. (1994). Emotional contagion. Cambridge: University Press. Krohne, H. W., Egloff, B., Kohlmann, C.-W. & Tausch, A. (1996). Untersuchungen mit einer deutschen Version der „Positive und Negative Affect Schedule“ (PANAS). Diagnostica, 42 (2), 139-156. Reicherts, M. & Horn, A. B. (2008). Emotionen im Sport. In W. Schlicht & B. Strauss (Eds.), Enzyklopädie der Psychologie. Grundlagen der Sportpsychologie (Bd. 1) (S. 563-633). Göttingen: Hogrefe.

Soziale Emotionsinduktion im Sport und deren Auswirkung auf die individuelle Leistung beim Lösen einer Gruppenaufgabe

In der Sportpsychologie gibt es bis anhin wenige Studien, welche sich mit dem Phänomen der sozialen Emotionsinduktion befassen (Reicherts & Horn, 2008). Die soziale Emotions-induktion ist ein Prozess, bei welchem der blosse emotionale Ausdruck einer Person ein emotionales Befinden bei einer anderen Person auslöst, welche diesen emotionalen Ausdruck wahrnimmt (McIntosh, Druckman & Zajonc, 1994). Von Apitzsch (2006) wird die soziale Emotionsinduktion in einem theoretischen Artikel als eine mögliche Ursache bezeichnet, warum es zu einem Kollaps von Teams im Sport kommen kann. Die vorliegende Arbeit untersucht die beiden Fragestellungen, ob es beim Lösen einer sportbezogenen Aufgabe unter Teammitgliedern überhaupt zu sozialer Emotionsinduktion kommt und welche Auswirkungen sich daraus für die individuelle Leistung der Teammitglieder ergeben. Zu diesem Zweck wur-den zwei experimentelle Studien mit unterschiedlicher Methodik durchgeführt: Im ersten Experiment mit Between-Subjects Design wurden die Versuchsperson (N = 81, ♀ = 38, M = 21.33 Jahre, SD = 1.45) zufällig einer der beiden experimentellen Bedingungen zugeordnet, wobei sie auf einen Konfidenten trafen, mit welchem sie ein gleichgeschlechtliches Ad Hoc Team bildeten. Als Team mussten sie eine Basketballaufgabe so schnell wie möglich lösen. Der Zwischensubjekt-Faktor des experimentellen Designs was der emotionale Ausdruck des Konfidenten mit positiver oder negativer Valenz und der Innersubjekt-Faktor, das emotionale Befinden der Versuchspersonen, welches prä- und postexperimentell mit der Positive and Negative Affect Schedule erfasst wurde (PANAS: Krohne, Egloff, Kohlmann & Tausch, 1996). Die Zweiergruppe wurde beim Lösen der Basketballaufgabe auf Video aufgenommen und die Anzahl der Frames, welche die Versuchspersonen zur Aufgabenlösung brauchten, wurde als individuelles Leistungsmass verwendet. Im zweiten Experiment wurden dem Konfidenten drei Versuchspersonen (N = 78, ♀ = 33, M = 20.88 Jahre, SD = 1.64) zugeordnet und als Gruppe durchliefen sie beide experimentellen Bedingungen, womit es sich also um ein Within-Subjects Design handelte. Das prä- und postexperimentelle Befinden der Versuchspersonen wurde mit dem Mehrdimensionalen Befindlichkeitsfragebogen erfasst (MDBF: Steyer, Schwenkmezger, Notz & Eid, 1997). Es zeigte sich in beiden Experimenten, dass das emotionale Befinden der Konfidenten von den Versuchspersonen sowie von Videoratern als unterschiedlich zwischen den Bedingungen wahrgenommen wurde (Manipulation-Check). Auch wenn sich eine Tendenz für eine soziale Emotionsinduktion teilweise zeigte, waren die durchgeführten, messwiederholten Varianzanalysen, welche die Auswirkungen der beiden experimentellen Bedingungen auf die Veränderung des emotionalen Befindens der Versuchspersonen prüfen sollten, nicht signifikant. Die durchgeführten t-Tests zeigten überdies, dass sich die Leistung der Versuchspersonen nicht zwischen den beiden experimentellen Bedingungen unterschied. Mit den beiden durchgeführten Experimenten konnten somit die Ergebnisse anderer experimenteller Studien zur sozialen Emotionsinduktion in Gruppen nicht repliziert werden (z.B. Barsade, 2002). Vor diesem Hintergrund wurden abschliessend methodische Änderungen diskutiert, welche eine Verbesserung der Vorgehensweise bei der Erfassung der sozialen Emotionsinduktion in Gruppen beim Lösen einer sportbezogenen Aufgabe zur Folge hätten.

White claimants and the moral community of South African land restitution

South African land restitution, by way of which the post-apartheid state compensates victims of racial land dispossession, has been intimately linked to former homelands: prototypical rural claims are those of communities that lost their rights in land when being forcibly relocated to reserves and they now aspire to return to their former lands and homes from their despised ‘homelands’. However, white farmers, who were also dispossessed (although usually compensated) by the apartheid state in the latter’s endeavour to consolidate existing homelands, have lodged restitution claims as well. While the Land Claims Court has principally admitted such restitution claims and ruled upon the merits of individual cases, state bureaucrats, legal activists, as well as other members of the public have categorically questioned and challenged such claims to land rights by whites. Focussing on white land claimaints effected by the establishment of former KwaNdebele, this paper investigates the contested field of moral entitlements emerging from divergent discourses about the true victims and beneficiaries of apartheid. It pays particular attention to land claims pertaining to the western frontier of KwaNdebele – the wider Rust de Winter area, which used to be white farmland expropriated in the mid-1980s for consolidation (that never occurred) and currently vegetates as largely neglected no-man’s-(state-)land under multiple land claims. Being the point of reference for state officials, former white farmers, Ndebele traditionalists, local residents, and other citizens, this homeland frontier is hence analysed as a fateful zone of contestation, in which the terms of a new South African moral community are negotiated.

A new light on an old disease: adhesion signaling in pemphigus vulgaris.

Disruption of desmosomal cadherin adhesion leads to the activation of intracellular signaling pathways that are responsible for blister formation in pemphigus vulgaris (PV). Recent studies corroborate the implication of the p38 mitogen-activated protein kinase in PV blistering via its downstream effector mitogen-activated protein kinase activated protein kinase 2. These insights highlight the key role of cadherins in tissue homeostasis and are expected to change pemphigus management.

Immune response in pemphigus and beyond: progresses and emerging concepts

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two severe autoimmune bullous diseases of the mucosae and/or skin associated with autoantibodies directed against desmoglein (Dsg) 3 and/or Dsg1. These two desmosomal cadherins, typifying stratified epithelia, are components of cell adhesion complexes called desmosomes and represent extra-desmosomal adhesion receptors. We herein review the advances in our understanding of the immune response underlying pemphigus, including human leucocyte antigen (HLA) class II-associated genetic susceptibility, characteristics of pathogenic anti-Dsg antibodies, antigenic mapping studies as well as findings about Dsg-specific B and T cells. The pathogenicity of anti-Dsg autoantibodies has been convincingly demonstrated. Disease activity and clinical phenotype correlate with anti-Dsg antibody titers and profile while passive transfer of anti-Dsg IgG from pemphigus patients' results in pemphigus-like lesions in neonatal and adult mice. Finally, adoptive transfer of splenocytes from Dsg3-knockout mice immunized with murine Dsg3 into immunodeficient mice phenotypically recapitulates PV. Although the exact pathogenic mechanisms leading to blister formation have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation, at least for PV. These new insights not only highlight the key role of Dsgs in maintenance of tissue homeostasis but are expected to progressively change pemphigus management, paving the way for novel targeted immunologic and pharmacologic therapies.