Thesis advisor: Thomas Chiles / Thesis advisor: James Kim / The purpose of this thesis is to describe some of the research I conducted in Dr. Markmann’s laboratory at Massachusetts General Hospital in the field of transplantation immunology. The first portion provides background information on the immune system and its different components, eventually providing an in-depth look at regulatory T cells, and their role in transplant immunology. The second portion of the thesis is dedicated to my experiments. This part presents the materials and methods used, the previous findings that led to my experiments, the data analysis and results, and a conclusive discussion. The research I did that is included in this thesis pertains to regulatory T cells. It is believed that a potential pathway to prolonging allograft survival is to drive antigen-specific CD4+Foxp3- T cells to convert to CD4+Foxp3+ T cells. I studied the effects of retinoic acid (RA) and anti-CD45RB treatment on Foxp3 expression in CD4+ T cells. These studies were done using different lines of transgenic mice that provided models of antigen-specificity. My in vitro data demonstrated that RA is capable of boosting TGF-β-mediated Foxp3 upregulation in a synergistic manner and that anti-CD45RB is also able to increase Foxp3 expression. In vivo RA experiments were inconclusive, and due to some misfortune and time constraints in vivo anti-CD45RB experiments were not conducted. Research funded by the following sources: 2R56AI048820, 5R01AI057851, and 5K01DK079207. / Thesis (BS) — Boston College, 2011. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: College Honors Program. / Discipline: Biology.

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The need for an unlimited source of islets and a safer method of immunosuppression has limited the widespread application of islet transplantation. To remedy the shortage of donor tissue, xenotransplantation of neonatal porcine islets (NPI) has been proposed. In this study we sought to determine if combining co-transplantation of NPI with Sertoli cells (SC) with a short-term monoclonal antibody (mAb) therapy would prevent NPI xenograft rejection. We hypothesize that this combination of treatments will lead to long-term NPI xenograft survival. Our result show a significant increase in the proportion of mice achieving long-term graft survival compared to untreated mice transplanted with NPI alone, as 7/7 mice treated with anti-LFA-1 mAb (p=0.001), 7/8 mice treated with anti-CD154 mAb (p=0.003), and 4/9 mice treated with anti-CD45RB mAb (p=0.020) achieved and maintained normoglycemia long-term. Therefore, we conclude that the combination of mAb therapy with SC is highly efficacious in preventing NPI xenograft rejection. / Experimental Surgery