No evidence was found for increased morbidity related to cholelithiasis or gallbladder abnormalities after renal transplantation. As in the general population, the risks associated with asymptomatic cholelithiasis do not appear to warrant prophylactic cholecystectomy for patients awaiting renal transplantation.

We previously showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) breaks tolerance induction. The objective of this study was to determine whether GM-CSF breaks established inhalation tolerance. To induce tolerance, BALB/c mice were exposed to aerosolized ovalbumin (OVA) for 10 consecutive days. A control group was exposed to saline. Subsequently, tolerant and control animals were exposed to OVA in a GM-CSF-enriched airway microenvironment. Tolerant animals, unlike control animals, did not develop airway and peripheral blood eosinophilia, had diminished levels of OVA-specific IgE, and reduced airway hyper-responsiveness. While tolerant animals did not express IL-4, IL-5 and IL-13, levels of the regulatory cytokines IL-10, IFN-c and transfoming growth factor (TGF)-b were similar between tolerant and non-tolerant animals. Lung CD4 + T cells were activated according to CD69, CD25 and T1/ST2 expression, but systemic responses characterized by splenocyte proliferation and Th2 effector function were dramatically reduced. Concurrent expression of GM-CSF and decorin, a natural inhibitor of TGF-b, reversed eosinophilic unresponsiveness. Our study suggests that the breakdown of tolerance and, by extension, the emergence of eosinophilic inflammation, requires two signals: one that triggers sensitization and one that interferes with negative regulation. Moreover, our study shows that dysregulated expression of an extracellular matrix protein may break established tolerance and lead to eosinophilic airway inflammation.

Background: Continuous exposure of sensitized mice to an innocuous antigen, such as OVA, does not lead to chronic airway eosinophilia, but induces antigen unresponsiveness and resolution of the inflammatory response. In this study we explored mechanisms underlying attenuation of the airway inflammatory response, assessed whether the phenomenon is strain-specific, and determined its consequences to airway physiology. Methods: Mice were sensitized and exposed to OVA for two and four weeks. Analysis involved BAL, flow cytometry, adoptive transfer of OVA specific CD4 T cells, ex vivo cytokine expression and response to methacholine challenge. Results: Chronic exposure to antigen resulted in decreased eosinophilia in 5 different mouse strains. Likewise, numbers of lung CD4 T cells expressing activation and Th2 markers sharply declined following continuous OVA exposure. Transfer studies using OVA TcR transgenic cells revealed that the contraction of lung T cells included antigen-specific cells. Systemically, we observed a loss of Th2 memory effector function. Finally, we observed significantly attenuated airway hyper-responsiveness (AHR) in chronically exposed animals. Conclusions: Attenuation of airway eosinophilia in response to chronic OVA exposure is independent of genetic background. Airway eosinophilia, but not systemic responses, correlates with and is predictive for airway hyperresponsiveness. Our study contributes to the understanding of immune regulatory processes controlling antigen-driven airway inflammatory responses.