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Alloreactive T lymphocytes can be primed through direct presentation of donor MHC:peptide complexes on graft cells and through indirect presentation of donor-derived determinants expressed by recipient APCs. The large numbers of determinants on an allograft and the high frequency of the alloreactive repertoire has further led to speculation that exposure to environmental Ags may prime T cells that cross-react with alloantigens. We sought to develop a model in which to test this hypothesis. We found that CD4+ T cells obtained from C57BL/6 (B6) mice that clinically resolved Leishmania major infection exhibited statistically significant cross-reactivity toward P/J (H-2p) Ags compared with the response to other haplotypes. B6 animals that were previously infected with L. major specifically rejected P/J skin grafts with second set kinetics compared with naive animals. Although donor-specific transfusion combined with costimulatory blockade (anti-CD40 ligand Ab) induced prolonged graft survival in naive animals, the same treatment was ineffective in mice previously infected with L. major. The studies demonstrate that cross-reactive priming of alloreactive T cells can occur and provide direct evidence that such T cells can have a significant impact on the outcome of an allograft. The results have important implications for human transplant recipients whose immune repertoires may contain cross-reactively primed allospecific T cells.

BackgroundConcerns about burnout, and its consequences, among German physicians are rising. However, data on burnout among German physicians are scarce. Also, a suspected association between burnout and German physicians’ wishes to leave remains to be studied. Therefore, the extent of burnout, and the association between burnout and wishes to leave clinical practice or to go abroad for clinical work was studied in a sample of young physicians in Saxony.MethodsIn a cross-sectional survey, all physicians ≤40 years and registered with the State Chamber of Physicians of Saxony, Germany (n = 5956) received a paper-pencil questionnaire inquiring about socio-demographics, job satisfaction, and wishes to leave clinical practice or to go abroad for clinical work. Response rate was 40 % (n = 2357). Burnout was measured with the German version of the Maslach Burnout Inventory - Human Services Survey (MBI) consisting of the subscales emotional exhaustion (feeling emotionally drained), depersonalization (feelings of cynicsm) and personal accomplishment (feelings of personal achievement in job). Variables associated with burnout, and the association between burnout and wishes to leave were assessed in multivariate logistic regression analyses.ResultsFor emotional exhaustion participants reached a mean of 21.3 [standard deviation = 9.74], for depersonalization a mean of 9.9 [5.92], and for personal accomplishment a mean of 36.3 [6.77]. Men exhibited significantly higher depersonalization than women (11.3 [6.11] versus 9 [5.62], p < 0.001). Eleven percent of participants showed a high degree of burnout on all subscales, while 35 % did not show a high degree of burnout on any subscale. Confirming that one would become a physician again, and higher satisfaction with the components “work environment” and “humaneness”, were associated with a lower chance for a high degree of burnout on all subscales. Higher emotional exhaustion and lower personal accomplishment were associated with an increased chance of wishing to leave clinical practice. Higher emotional exhaustion and higher depersonalization were associated with an increased chance of wishing to go abroad for clinical work.ConclusionsPreventing physician burnout may not only benefit the affected individual. It may also benefit the health care system by potentially preventing physicians from leaving clinical practice or from going abroad for clinical work.

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ObjectiveStudies from the USA have identified medical students as a major source of stigmatizing attitudes towards overweight and obese individuals. As data from Europe is scarce, medical students’ attitudes were investigated at the University of Leipzig in Leipzig, Germany.DesignCross-sectional survey containing an experimental manipulation consisting of a pair of vignettes depicting an obese and a normal weight 42-year-old woman, respectively. Vignettes were followed by the Fat Phobia Scale (FPS), a semantic differential assessing weight related attitudes. In case of the overweight vignette a panel of questions on causal attribution for the overweight preceded administration of the FPS.Subjects671 medical students were enrolled at the University of Leipzig from May to June 2011.ResultsThe overweight vignette was rated significantly more negative than the normal weight vignette (mean FPS score 3.65±0.45 versus 2.54±0.38, p<0.001). A higher proportion of students had negative attitudes towards the overweight as compared to the normal weight individual (98.9% versus 53.7%, p<0.001). A “positive energy balance” was perceived as the most relevant cause for the overweight, followed by “negligent personality trait”, “societal and social environment” and “biomedical causes”. Attributing a “positive energy balance” or “negligent personality trait” as relevant cause for the overweight was positively associated with negative attitudes.ConclusionThe results of this study confirm and complement findings from other countries, mainly the USA, and indicate that weight bias in the health care setting may be a global issue. Stigmatizing attitudes towards overweight and obesity are prevalent among a sample of medical students at the University of Leipzig. Negative attitudes arise on the basis of holding the individual accountable for the excess weight. They call for bringing the topic of overweight and obesity more into the focus of the medical curriculum and for enhancing medical students’ awareness of the complex aetiology of this health condition.