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.

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(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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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University of Chicago
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Khiew, Stella H; Yang, Jinghui; Young, James S et al. (2017) CTLA4-Ig in combination with FTY720 promotes allograft survival in sensitized recipients. JCI Insight 2:
Chong, Anita S (2017) Alone Again, Naturally: B Cells Encountering Antigen Without T cells. Transplantation 101:1956-1958
Young, James S; McIntosh, Christine; Alegre, Maria-Luisa et al. (2017) Evolving Approaches in the Identification of Allograft-Reactive T and B Cells in Mice and Humans. Transplantation 101:2671-2681
Miller, Michelle L; Alegre, Maria-Luisa; Chong, Anita S (2017) Transplantation tolerance after allograft rejection. Curr Opin Organ Transplant 22:64-70
Young, J S; Daniels, M D; Miller, M L et al. (2017) Erosion of Transplantation Tolerance After Infection. Am J Transplant 17:81-90
Lei, Yuk Man; Chen, Luqiu; Wang, Ying et al. (2016) The composition of the microbiota modulates allograft rejection. J Clin Invest 126:2736-44
Alegre, Maria-Luisa; Lakkis, Fadi G; Morelli, Adrian E (2016) Antigen Presentation in Transplantation. Trends Immunol 37:831-843
Young, J S; Chen, J; Miller, M L et al. (2016) Delayed Cytotoxic T Lymphocyte-Associated Protein 4-Immunoglobulin Treatment Reverses Ongoing Alloantibody Responses and Rescues Allografts From Acute Rejection. Am J Transplant 16:2312-23
Miller, M L; Chen, J; Daniels, M D et al. (2016) Adoptive Transfer of Tracer-Alloreactive CD4+T Cell Receptor Transgenic T Cells Alters the Endogenous Immune Response to an Allograft. Am J Transplant 16:2842-2853
Yang, Jinghui; Chen, Jianjun; Young, James S et al. (2016) Tracing Donor-MHC Class II Reactive B cells in Mouse Cardiac Transplantation: Delayed CTLA4-Ig Treatment Prevents Memory Alloreactive B-Cell Generation. Transplantation 100:1683-91

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