The purpose of this core is to provide essential common facilities and expertise for the immunopathological studies in all 3 projects. The primary role is to document and characterize: 1) The status of the heart, lung, kidney and skin allografts (nature of infiltrate, presence of acute or chronic rejection, including a humoral component and the quantitation of lesions. 2) Systemic effects of the protocols (toxicity, complications, BK viral infection, PTLD) 3) Intragraft markers that predict acceptance vs. rejection 4) Mechanisms by which intragraft cells may promote rejection or acceptance The pathology studies in Core A are essential to evaluate the status of the allografts, particularly the in situ events in the heart, lung and kidney grafts. The studies are critical to determine the nature and location of the cells infiltrating the graft, the role of antibodies in rejection and systemic toxicity of treatment. The techniques that will be utilized include routine histology, immunohistochemistry, immunofluorescence, and electron microscopy. Immunoperoxidase techniques with a panel of mAbs will distinguish the infiltrating cell types (Teff, Treg, Breg, et al), adhesion and cytokine molecules and receptors, complement deposition (C4d), and endothelial activation markers (e.g., pERK). Analysis will be enhanced by whole slide digital scans and morphometry. The pathology results will be correlated with functional and molecular studies done in the projects. In addition, complete necropsies will be done on all animals, with samples from all major organs analyzed by routine and special techniques as indicated.
The goal of this research is to develop a clinically relevant strategy to induce tolerance of heart and lung transplants, by testing approaches in non-human primates and mice. If this can be achieved, organs could be transplanted in humans with success and without the complications of long term immunosuppressive therapy.
| Wang, Zhaohui; Louras, Nathan J; Lellouch, Alexandre G et al. (2018) Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4+ Treg in nonhuman primates. Mol Oncol 12:1374-1382 |
| Newton, Ryan H; Shrestha, Sharad; Sullivan, Jenna M et al. (2018) Maintenance of CD4 T cell fitness through regulation of Foxo1. Nat Immunol 19:838-848 |
| Hotta, Kiyohiko; Oura, Tetsu; Dehnadi, Abbas et al. (2018) Long-term Nonhuman Primate Renal Allograft Survival Without Ongoing Immunosuppression in Recipients of Delayed Donor Bone Marrow Transplantation. Transplantation 102:e128-e136 |
| 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 |
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