title: The effect of IL-2, IL-12 and IL15 on the function of natural killer cells in children suffering from type 1 diabetes mellitus.
abstract: BACKGROUND
  The immunologic reaction of pancreatic islets destruction leads to the occurrence of type 1 diabetes mellitus (T1D). The autoreactive lymphocytes play the pivotal role in this process although mechanisms regulating the lymphocyte migration and infiltration of Langerhans islets have not been fully understood yet. The in vitro studies showed natural killer (NK) cells potency to initiate pancreatic islets cell lyses. Many authors postulate that NK cells may be involved in this reaction.
  
  
  OBJECTIVE
  The aim of the study was to evaluate the effect of IL-2, IL-12 and IL-15 stimulation on peripheral blood NK cells in children suffering from type 1 diabetes mellitus in comparison to healthy controls.
  
  
  METHODS
  Fifteen children with type 1 diabetes and 10 healthy adults were examined. NK cells were isolated by the magnetic cell separation system (MACS). For activation, NK cells were cultured with IL-2, IL-12 and IL-15 for 24 hours. The production of IFN-γ and IL-10 by NK cells was measured using commercial ELISA kits. FACS analysis of cell surface antigens--CD16, CD56, NKG2D and CD137 was performed using LSR II flow cytometer.
  
  
  RESULTS
  In children with T1D the IFN-γ median concentration in supernatant obtained from NK cells culture was 16.831 ng/ml (inter quartile range 5.566-25.509) and did not statistically differ from median IFN-γ concentration in the control group--14.810 ng/ml (7.022-18.785), p = 0.76. In contrast, the IL-10 median concentration was statistically higher in T1D patients 7.87 pg/ml (1.32-11.37) than in healthy participants--1.41 pg/ml (1.05-4.81), p = 0.01. The median (inter-quartile range) percentage of NK NKG2D(+) was found in 0.42% (0.28-0.76) cells of TID patients versus 0.72% (0.53-1.08) in the controls (p = 0.05). There was no difference between -T1D group and the control group in regard to NK cells expressing CD137 - 6.58% (3.38-12.4) versus 6.85% (2.94-10.8); p = 0.8.
  
  
  CONCLUSIONS
  The observed activity of NK cells after in vitro stimulation by IL2, IL-12 and IL15 in children suffering from type 1 diabetes mellitus indicates the tendency for supporting the inhibition of autoimmunological reaction by increased IL10 synthesis and increased number of NK cells with surface NKG2D receptors.
authors.affiliation: Department of Kidney Transplantation, Medical University of Lodz, Poland. slawomir.chrul@umed.lodz.pl
authors.forename: Sławomir
authors.initials: S
authors.lastname: Chrul
authors.forename: Ewa
authors.initials: E
authors.lastname: Polakowska
authors.forename: Marcin
authors.initials: M
authors.lastname: Mycko
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fendler
authors.forename: Rafał
authors.initials: R
authors.lastname: Zwiech
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szadkowska
mesh_terms: D000293:Adolescent; D002478:Cells, Cultured; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000378:metabolism*; D019409:Interleukin-15 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism
chemical_list: D019409:Interleukin-15; D007376:Interleukin-2; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016753:Interleukin-10; D018664:Interleukin-12