Core B will provide key facilities and expertise for the mechanistic studies in Projects 1 and 2. Understanding the mechanisms underlying rejection and tolerance of heart and lung transplants in the primate experiments described in Projects 1 and 2 will not only help us achieve tolerance but will help us recognize when it is present or absent. The following methodologies will be utilized: 1. Determine the role of MHC disparities on alloresponses by MHC genotyping of donor and recipient monkeys; 2. Investigate the contributions of direct and indirect T cell alloresponses and autoimmune responses to acute/chronic graft rejection; 3. Monitor the frequency, phenotype, antigen specificity, and functions of donor-specific memory T cells present in blood and lymphoid organs of monkeys tested pre- and post-transplantation; 4. Monitor the frequency, phenotype, antigen specificity, and mechanisms of action of regulatory T cells and expand these cells in vitro for adoptive transfers experiments; 5. Analyze B cell subsets and antibodies as well as their functional properties; 6. Monitor pro- and anti-inflammatory cytokines in sera. The knowledge acquired from these experiments will be used to optimize mixed chimerism protocols designed to achieve tolerance of heart and lungs allografts and to assist in the successful translation of those tolerance protocols to the clinic.
The goal of Core B is to characterize the cells, soluble factors, and immune mechanisms implicated in the induction and maintenance of tolerance (indefinite survival of transplants without immunosuppression) to heart and lung transplants. Understanding the mechanisms by which tolerance is induced and maintained will contribute to the successful application of tolerance protocols to human heart and lung transplant recipients.
| Robinson, Kortney A; Orent, William; Madsen, Joren C et al. (2018) Maintaining T cell tolerance of alloantigens: Lessons from animal studies. Am J Transplant 18:1843-1856 |
| Sasaki, Hajime; Oura, Tetsu; Spitzer, Thomas R et al. (2018) Preclinical and clinical studies for transplant tolerance via the mixed chimerism approach. Hum Immunol 79:258-265 |
| Tanimine, Naoki; Turka, Laurence A; Priyadharshini, Bhavana (2018) Navigating T-Cell Immunometabolism in Transplantation. Transplantation 102:230-239 |
| Michel, S G; Madariaga, M L L; LaMuraglia 2nd, G M et al. (2018) The effects of brain death and ischemia on tolerance induction are organ-specific. Am J Transplant 18:1262-1269 |
| Smith, R N; Adam, B A; Rosales, I A et al. (2018) RNA expression profiling of renal allografts in a nonhuman primate identifies variation in NK and endothelial gene expression. Am J Transplant 18:1340-1350 |
| Chatterjee, Debanjana; Moore, Carolina; Gao, Baoshan et al. (2018) Prevalence of polyreactive innate clones among graft--infiltrating B cells in human cardiac allograft vasculopathy. J Heart Lung Transplant 37:385-393 |
| Gonzalez-Nolasco, Bruno; Wang, Mengchuan; Prunevieille, Aurore et al. (2018) Emerging role of exosomes in allorecognition and allograft rejection. Curr Opin Organ Transplant 23:22-27 |
| Smith, R N; Matsunami, M; Adam, B A et al. (2018) RNA expression profiling of nonhuman primate renal allograft rejection identifies tolerance. Am J Transplant 18:1328-1339 |
| Fan, Martin Y; Low, Jun Siong; Tanimine, Naoki et al. (2018) Differential Roles of IL-2 Signaling in Developing versus Mature Tregs. Cell Rep 25:1204-1213.e4 |
| Benichou, Gilles; Prunevieille, Aurore (2018) Graft-derived exosomes. When small vesicles play a big role in transplant rejection. Am J Transplant 18:1585-1586 |
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