title: Cord blood CD4+ T cells respond to self heat shock protein 60 (HSP60).
abstract: BACKGROUND
  To prevent harmful autoimmunity most immune responses to self proteins are controlled by central and peripheral tolerance. T cells specific for a limited set of self-proteins such as human heat shock protein 60 (HSP60) may contribute to peripheral tolerance. It is not known whether HSP60-specific T cells are present at birth and thus may play a role in neonatal tolerance. We studied whether self-HSP60 reactive T cells are present in cord blood, and if so, what phenotype these cells have.
  
  
  RESULTS
  Cord blood mononuclear cells (CBMC) of healthy, full term neonates (n = 21), were cultured with HSP60 and Tetanus Toxoid (TT) to study antigen specific proliferation, cytokine secretion and up-regulation of surface markers. The functional capacity of HSP60-induced T cells was determined with in vitro suppression assays. Stimulation of CBMC with HSP60 led to CD4(+) T cell proliferation and the production of various cytokines, most notably IL-10, Interferon-gamma, and IL-6. HSP60-induced T cells expressed FOXP3 and suppressed effector T cell responses in vitro.
  
  
  CONCLUSIONS
  Self-reactive HSP60 specific T cells are already present at birth. Upon stimulation with self-HSP60 these cells proliferate, produce cytokines and express FOXP3. These cells function as suppressor cells in vitro and thus they may be involved in the regulation of neonatal immune responses.
authors.affiliation: Department of Pediatric Immunology, Wilhelmina Children's Hospital, Utrecht, The Netherlands. jaalber2@umcutrecht.nl
authors.forename: Joost A
authors.initials: JA
authors.lastname: Aalberse
authors.forename: Berber
authors.initials: B
authors.lastname: Kapitein
authors.forename: Sytze
authors.initials: S
authors.lastname: de Roock
authors.forename: Mark R
authors.initials: MR
authors.lastname: Klein
authors.forename: Wilco
authors.initials: W
authors.lastname: de Jager
authors.forename: Ruurd
authors.initials: R
authors.lastname: van der Zee
authors.forename: Maarten O
authors.initials: MO
authors.lastname: Hoekstra
authors.forename: Femke
authors.initials: F
authors.lastname: van Wijk
authors.forename: Berent J
authors.initials: BJ
authors.lastname: Prakken
mesh_terms: D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology
chemical_list: D001324:Autoantigens; D018834:Chaperonin 60; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015850:Interleukin-6; D016753:Interleukin-10; D007371:Interferon-gamma