Birte Pantenburg

Primed allospecific T cells prevent the effects of costimulatory blockade on prolonged cardiac allograft survival in mice.

Costimulatory blockade can induce long‐term allograft survival in naïve animals, but may not be as effective in animals with previously primed immune repertoires. We attempted to induce long‐term graft survival in B10.D2 recipients of B10.A cardiac allografts using donor‐specific transfusion (DST) plus anti‐CD40 ligand antibody (αCD40L). Recipients were either naïve mice, or mice previously primed to B10.A or third party alloantigens through engraftment and rejection of skin transplants. Untreated naïve mice rejected cardiac transplants by day 15 and contained a high frequency of primed, donor‐reactive T cells. Donor‐specific transfusion/αCD40L treatment of naïve animals induced long‐term graft survival associated with low frequencies of donor‐reactive T cells. Previous priming of donor‐specific T cells through rejection of B10.A, but not third party, skin grafts prevented the effects of DST/αCD40L on prolonging survival of B10.A hearts. Moreover, adoptive transfer of CD3+, CD4+ or CD8+ T cells from B10.A skin‐graft‐primed animals prevented the effects of DST/αCD40L. The data demonstrate that animals with immune repertoires containing previously primed, donor‐reactive T cells are resistant to the effects of costimulatory blockade. The findings have important implications for ongoing, costimulatory blockade‐based trials in humans, whose T‐cell repertoires are known to contain memory alloreactive T cells.

T Cells Primed by Leishmania major Infection Cross-React with Alloantigens and Alter the Course of Allograft Rejection

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.

Medical Students’ Attitudes towards Overweight and Obesity

Objective Studies 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. Design Cross-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. Subjects 671 medical students were enrolled at the University of Leipzig from May to June 2011. Results The 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. Conclusion The 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.

Feeding of Young Children during Diarrhea: Caregivers' Intended Practices and Perceptions

Childhood diarrhea is an important cause of malnutrition, which can be worsened when caretakers limit nutritional support. We queried 390 caregivers and their children in a peri-urban community in Lima, Peru regarding general perceptions of feeding and feeding practices during diarrhea. Overall, 22.1% of caregivers perceived feeding during diarrhea to be harmful. At baseline, 71.9% of caregivers would discontinue normal feeding or give less food. Most would withhold milk, eggs, and meats. Approximately 40% of caregivers would withhold vegetables and fruits. A pilot educational intervention was performed to improve feeding during diarrhea. At follow-up survey 3 months later, none of the caregivers would recommend withholding food. Only 23.2% would recommend discontinuing normal feeding and 1.8% perceived food to be damaging. Misperceptions of the role of feeding during diarrhea pose a significant health risk for children, but a simple educational intervention might have a major impact on these perceptions and practices.