title: Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques.
abstract: In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease.
authors.affiliation: Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, OR, USA.
authors.forename: C
authors.initials: C
authors.lastname: Meyer
authors.affiliation: Department of Radiation Medicine, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: J
authors.initials: J
authors.lastname: Walker
authors.affiliation: Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, OR, USA.
authors.forename: J
authors.initials: J
authors.lastname: Dewane
authors.affiliation: Division of Biomedical Sciences, University of California-Riverside, Riverside, CA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Engelmann
authors.affiliation: Department of Radiation Medicine, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: W
authors.initials: W
authors.lastname: Laub
authors.affiliation: Department of Radiation Medicine, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: S
authors.initials: S
authors.lastname: Pillai
authors.affiliation: Department of Radiation Medicine, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Thomas
authors.affiliation: Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, OR, USA.|Division of Biomedical Sciences, University of California-Riverside, Riverside, CA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Messaoudi
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000528:radiation effects; D007107:Immune System / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008253:Macaca mulatta / Q000821:virology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D016559:Tacrolimus / Q000494:pharmacology; D018140:Varicellovirus / Q000187:drug effects / Q000254:growth & development / Q000528:radiation effects; D019562:Viral Load / Q000187:drug effects / Q000528:radiation effects; D014775:Virus Activation / Q000187:drug effects / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000379:methods*
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus
keywords: CD3 immunotoxin; Janus activated kinase inhibitor simian varicella virus; anti-thymocyte globulin; immune system; irradiation; prednisone; rhesus macaque; tacrolimus