title: The rejuvenating effects of leuprolide acetate on the aged baboon's thymus.
abstract: BACKGROUND
  We have previously demonstrated that the juvenile thymus plays an essential role in tolerance induced by both renal transplantation and a short course of calcineurin inhibitors. Aged thymi have a decreased ability to induce tolerance. Luteinizing hormone-releasing hormone (LHRH) is known to pharmacologically rejuvenate the thymus in rodents. In order to develop a clinically applicable regimen of transplantation tolerance in adults, we sought to determine if thymic rejuvenation would occur with LHRH agonism in non-human primates.
  
  
  RESULTS
  Thymic rejuvenation was evaluated by magnetic resonance imaging (MRI), histology, as well as in-vitro cellular and molecular tests. Four aged male hamadryas baboons underwent subcutaneous injection of a 3-month depot of Lupron (11.25mg; LI) and were followed for 3 months. Thymi increased volumetrically by MRI. After LI, thymic cellularity markedly increased within the cortical and medullary thymus. Additionally, a significant increase in the CD4(+)/CD45RA(hi+) population in the peripheral blood occurred for 50 days after LI, and flow cytometry of thymic tissue revealed a large increase in the percentage of CD4(+)/CD8(+) cells. TREC assay corroborated enhancement in thymic function.
  
  
  CONCLUSIONS
  These data indicate that LI is associated with thymic rejuvenation in baboons, and further confirm that extrinsic factors play an important role in thymic rejuvenation in a non-human primate model.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, United States; Harvard Medical School, Boston, MA 02129, United States.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Scalea
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, United States; Harvard Medical School, Boston, MA 02129, United States.
authors.forename: Radbeh
authors.initials: R
authors.lastname: Torabi
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, United States; Harvard Medical School, Boston, MA 02129, United States.
authors.forename: Aseda
authors.initials: A
authors.lastname: Tena
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, United States; Harvard Medical School, Boston, MA 02129, United States.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tasaki
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, United States; Harvard Medical School, Boston, MA 02129, United States.
authors.forename: Bradford C
authors.initials: BC
authors.lastname: Gillon
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, United States; Harvard Medical School, Boston, MA 02129, United States.
authors.forename: Shannon
authors.initials: S
authors.lastname: Moran
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, United States; Harvard Medical School, Boston, MA 02129, United States.
authors.forename: Taylor
authors.initials: T
authors.lastname: Cormack
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, United States; Harvard Medical School, Boston, MA 02129, United States.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Villani
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, United States; Harvard Medical School, Boston, MA 02129, United States.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, United States; Harvard Medical School, Boston, MA 02129, United States.
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, United States; Harvard Medical School, Boston, MA 02129, United States.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D007108:Immune Tolerance; D017493:Leukocyte Common Antigens / Q000378:metabolism; D016729:Leuprolide / Q000008:administration & dosage* / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D010215:Papio; D012060:Rejuvenation; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D007987:Gonadotropin-Releasing Hormone; D017493:Leukocyte Common Antigens; D016729:Leuprolide
keywords: Baboons; LHRH agonist; Thymic rejuvenation