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Biol Blood Marrow Transplant ; 21(10): 1732-8, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26210443

ABSTRACT

Post-transplant lymphoproliferative disease (PTLD) is a major complication of clinical organ and cell transplantation. Conditioning and immunosuppressive regimens that significantly impair T cell immunity, including depleting antibodies and calcineurin inhibitors, increase the risk of PTLD after transplantation. Swine PTLD has been shown to closely resemble human PTLD in morphology, histology, and viral-driven reactivation of B cells. Previously, we reported high incidences of PTLD after hematopoietic cell transplantation (HCT) in miniature swine recipients conditioned with thymic irradiation (TI) in addition to T cell depletion and cyclosporine A monotherapy after transplantation. Replacement of TI with 100 cGy of total body irradiation resulted in similar numbers of B cells early post-transplantation, greater numbers of T cells at day 0, and markedly decreased incidence of PTLD, suggesting that a threshold number of T cells may be necessary to prevent subsequent B cell proliferation and development of overt PTLD. Results from this large cohort of animals provide insight into the important effect of irradiation and T cell immunity on the incidence of PTLD after HCT and reinforce the pig model as a valuable tool for the study of PTLD and HCT.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Immunosuppressive Agents/adverse effects , Lymphatic Irradiation/adverse effects , Lymphoproliferative Disorders/prevention & control , Swine, Miniature , Thymus Gland/radiation effects , Transplantation Conditioning/adverse effects , Whole-Body Irradiation , Animals , Calcineurin Inhibitors/adverse effects , Calcineurin Inhibitors/therapeutic use , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Disease Models, Animal , Graft vs Host Disease/immunology , Graft vs Host Disease/veterinary , Herpesvirus 1, Suid/pathogenicity , Histocompatibility , Humans , Immunosuppressive Agents/therapeutic use , L-Lactate Dehydrogenase/blood , Lymphatic Irradiation/methods , Lymphocyte Depletion/adverse effects , Lymphoproliferative Disorders/etiology , Lymphoproliferative Disorders/veterinary , Swine , Swine Diseases/etiology , Swine Diseases/prevention & control , Swine Diseases/virology , Swine, Miniature/immunology , Swine, Miniature/virology , T-Lymphocytes/radiation effects , Transplantation Conditioning/methods , Tumor Virus Infections/veterinary , Whole-Body Irradiation/adverse effects
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