title: Sirolimus enhances the magnitude and quality of viral-specific CD8+ T-cell responses to vaccinia virus vaccination in rhesus macaques.
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.
authors.affiliation: Emory Transplant Center, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Turner
authors.forename: V O
authors.initials: VO
authors.lastname: Shaffer
authors.forename: K
authors.initials: K
authors.lastname: Araki
authors.forename: C
authors.initials: C
authors.lastname: Martens
authors.forename: P L
authors.initials: PL
authors.lastname: Turner
authors.forename: S
authors.initials: S
authors.lastname: Gangappa
authors.forename: M L
authors.initials: ML
authors.lastname: Ford
authors.forename: R
authors.initials: R
authors.lastname: Ahmed
authors.forename: A D
authors.initials: AD
authors.lastname: Kirk
authors.forename: C P
authors.initials: CP
authors.lastname: Larsen
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000276:immunology / Q000627:therapeutic use; D008253:Macaca mulatta; D020123:Sirolimus / Q000276:immunology / Q000627:therapeutic use*; D014611:Vaccination; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D014765:Viral Vaccines; D020123:Sirolimus