Critical issues emerging from current attempts at inducing transplantation tolerance in the clinic include the need for biomarkers that predict and diagnose tolerance as well as for the identification of barriers to tolerance induction and maintenance. Our preliminary observations have led us to the realization that the durability of the tolerant state is variable and can be unpredictably breached by Listeria infections. The overall goal of the proposed studies Is to determine a mechanistic basis for how Infections can either erode or transiently abrogate robust tolerance after It has been stably established.

Public Health Relevance

(Relevance) Successful induction of transplantation tolerance for achieving long-term allograft survival has been reported in a number of preclinical models and in limited clinical scenarios. 777e overall goal of the proposed studies Is to determine a mechanistic basis for how infections with Listeria and other Infections erode or abrogate tolerance after It has been well and stably established through co-stimulation blockade. Insights gained from these studies may lead to new approaches for establishing, maintaining and restoring the state of tolerance in transplantation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI097113-02
Application #
8512661
Study Section
Special Emphasis Panel (ZAI1-MFH-I)
Project Start
2013-07-01
Project End
2017-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$370,802
Indirect Cost
$135,802
Name
University of Chicago
Department
Type
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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Chong, Anita S; Alegre, Maria-Luisa (2014) Transplantation tolerance and its outcome during infections and inflammation. Immunol Rev 258:80-101
Cowan, Michelle; Chon, W James; Desai, Amishi et al. (2014) Impact of immunosuppression on recall immune responses to influenza vaccination in stable renal transplant recipients. Transplantation 97:846-53
Chen, J; Yin, H; Xu, J et al. (2013) Reversing endogenous alloreactive B cell GC responses with anti-CD154 or CTLA-4Ig. Am J Transplant 13:2280-92
Montgomery, Christopher P; Daniels, Melvin D; Zhao, Fan et al. (2013) Local inflammation exacerbates the severity of Staphylococcus aureus skin infection. PLoS One 8:e69508