title: Sleep influences the immune response and the rejection process alters sleep pattern: Evidence from a skin allograft model in mice.
abstract: BACKGROUND
  Sleep generally regulates immune functions in a supportive manner and can affect parameters that are directly involved in the rejection process.
  
  
  OBJECTIVE
  The first objective was to assess whether sleep deprivation (SD) or sleep restriction (SR) affects the allograft rejection process in mice. The second objective was to investigate whether the rejection process itself modulates the sleep pattern of allografted mice.
  
  
  METHODS
  Adult BALB/c and C57BL/6J male mice were used as the donors and recipients, respectively, except for the syngeneic group (ISOTX), which received skin from mice of the same strain (C57BL/6J). The recipients were randomly assigned to either one of two control groups - TX (allogenic) or ISOTX (syngeneic) - which underwent stereotaxic surgery to enable sleep recording prior to the allograft but were not sleep deprived; one of two paradoxical sleep deprived groups - SDTX and TXSD - which underwent 72h of continuous SD either before or after the allograft respectively, and one of two sleep restricted groups - SRTX and TXSR - which underwent 21h of SD and 3h of sleep for 15days either before or after the allograft respectively.
  
  
  METHODS
  The skin allograft was inspected daily to determine the survival time, expected as 8.0±0.4days in this transplant model under no treatment. The sleep pattern was controlled throughout the rejection process in the SD and SR groups. Draining lymph nodes, spleen, blood and skin grafts were harvested on the 5th day after transplantation for evaluation of the immune parameters related to allograft rejection.
  
  
  RESULTS
  In the control groups, we observed a reduction in paradoxical sleep throughout the entire allograft rejection process. Acute and chronic experimental sleep loss in the SD and SR groups produced marked alterations in the immune response. Both SD and SR prolonged allograft survival compared to the non-sleep-deprived group. There were reductions in the following parameters involved in the allograft rejection under sleep loss: CD4+and CD8+T cell subpopulations in the peripheral lymph organs and spleen, circulating sIL-2R levels, graft-infiltrating CD4+T cells and skin allograft global gene expression.
  
  
  CONCLUSIONS
  We provide, as far as we are aware, the first evidence in vivo that the immune response can alter the normal sleep pattern, and that sleep loss can conversely affect the immune response related to graft rejection.
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Francieli Silva
authors.initials: FS
authors.lastname: Ruiz
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil. Electronic address: ml.andersen12@gmail.com.
authors.forename: Monica Levy
authors.initials: ML
authors.lastname: Andersen
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Guindalini
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Leandro Pires
authors.initials: LP
authors.lastname: Araujo
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: José Daniel
authors.initials: JD
authors.lastname: Lopes
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Tufik
mesh_terms: D064591:Allografts; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006084:Graft Rejection / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D016038:Skin Transplantation; D012890:Sleep / Q000502:physiology*; D012893:Sleep Wake Disorders / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*
keywords: Allograft; Cytokines; Gene expression; Immune system; Mice; Sleep; Sleep deprivation; T cells; Transplant; Transplantation