Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques

C. Meyer, J. Walker, J. Dewane, F. Engelmann, W. Laub, S. Pillai, Charles R. Thomas, I. Messaoudi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)491-510
Number of pages20
JournalClinical and Experimental Immunology
Volume181
Issue number3
DOIs
StatePublished - Sep 1 2015
Externally publishedYes

Keywords

  • Anti-thymocyte globulin
  • CD3 immunotoxin
  • Immune system
  • Irradiation
  • Janus activated kinase inhibitor simian varicella virus
  • Prednisone
  • Rhesus macaque
  • Tacrolimus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Meyer, C., Walker, J., Dewane, J., Engelmann, F., Laub, W., Pillai, S., Thomas, C. R., & Messaoudi, I. (2015). Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques. Clinical and Experimental Immunology, 181(3), 491-510. https://doi.org/10.1111/cei.12646