@article{Transplantation:6513,
      recid = {6513},
      author = {Allocco, Jennifer Brianne},
      title = {Duration of Alloantigen Expression Affects the Induction  of Transplantation Tolerance},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2023-06},
      abstract = {Although transplantation is the treatment of choice for  end stage organ failure, transplanted organs are vulnerable  to immune-mediated rejection. To prevent rejection,  patients are maintained on a strict immunosuppressive  regimen; however, immunosuppression is costly, and the side  effects associated with continuing life-long  immunosuppression are numerous and unpleasant, leading to  patient noncompliance. Current research efforts aim to  replace conventional immunosuppression with short-term  treatments inducing donor-specific immune tolerance, which  would mean a patient is only nonresponsive to  transplant-derived antigen and would retain their ability  to mount immune responses to other antigens, such as those  from infections and malignancies. Although possible to  achieve in patients, donor-specific tolerance is rare and  remains vulnerable to inflammatory challenges capable of  precipitating transplant rejection. In this dissertation,  we investigated vulnerabilities to donor-specific  transplantation tolerance during both the induction and  maintenance phases of tolerance. We identified functional  heterogeneity within the transplant-reactive T cell  compartment, dependent upon the length of their cognate  antigen exposure in the context of immunosuppression:  persistent antigen promoted T cell dysfunction whereas T  cells specific for non-persistent antigens retained  function. By forcing antigen exposure, we promoted  widespread T cell dysfunction and protected the transplant  recipients from infection-mediated rejection. We also  investigated the memory T cell response following treatment  with persistent antigen and immunosuppression and  identified that memory T cells can develop a degree of  dysfunction, although not to the same extent as naïve T  cells. As robust allospecific T cell dysfunction is a  hallmark of tolerance and desirable in patients, these  findings may inform future strategies to promote clinical  transplantation tolerance. },
      url = {http://knowledge.uchicago.edu/record/6513},
      doi = {https://doi.org/10.6082/uchicago.6513},
}