Sirolimus enhances the magnitude and quality of viral-specific CD8+ T-cell responses to vaccinia virus vaccination in rhesus macaques

Am J Transplant. 2011 Mar;11(3):613-8. doi: 10.1111/j.1600-6143.2010.03407.x.

Abstract

Sirolimus is a potent antiproliferative agent used clinically to prevent renal allograft rejection. However, little is known about the effects of maintenance immunosuppressive agents on the immune response to potentially protective vaccines. Here we show that sirolimus paradoxically increases the magnitude and quality of the CD8+ T-cell response to vaccinia vaccination in nonhuman primates, fostering more robust recall responses compared to untreated and tacrolimus-treated controls. Enhancement of both the central and effector memory compartments of the vaccinia-specific CD8+ T-cell response was observed. These data elucidate new mechanistic characteristics of sirolimus and suggest immune applications extending beyond its role as an immunosuppressant.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cytokines / metabolism
  • Flow Cytometry
  • Immunologic Memory / drug effects
  • Immunologic Memory / immunology*
  • Immunosuppressive Agents / immunology
  • Immunosuppressive Agents / therapeutic use
  • Macaca mulatta
  • Sirolimus / immunology
  • Sirolimus / therapeutic use*
  • Vaccination
  • Vaccinia / immunology
  • Vaccinia / prevention & control*
  • Vaccinia / virology
  • Vaccinia virus / immunology
  • Viral Vaccines / immunology
  • Viral Vaccines / therapeutic use*

Substances

  • Cytokines
  • Immunosuppressive Agents
  • Viral Vaccines
  • Sirolimus