title: Release of soluble CD30 after allogeneic stimulation is mediated by memory T cells and regulated by IFN-γ and IL-2.
abstract: BACKGROUND
  Membrane CD30 is an important costimulatory molecule for activated T lymphocytes, and serum level of soluble CD30 (sCD30) is considered a marker for predicting outcome in kidney transplantation.
  
  
  METHODS
  We investigated the kinetics of CD30 expression on CD4 and CD8 T-cell populations and the source of sCD30 during alloimmune responses in vitro. The effect of neutralizing antibodies against interferon (IFN)-γ and other cytokines on sCD30 release and the involvement of metalloproteinases ADAM10 and ADAM17/TACE that are responsible for sCD30 shedding were also assessed. Memory phenotypes and CD30 expression on allostimulated CD3 lymphocytes were evaluated in dialysis patients and matched controls.
  
  
  RESULTS
  Allogeneic stimulation resulted in conversion of naive responder cells to central memory CD4 cells (P<0.001 at 96 hr) and effector CD8 cells (P<0.01 at 120 hr), which was accompanied by increased CD30 expression. Release of sCD30 was attributed mainly to central memory cells, and neutralization of IFN-γ (P<0.001) and interleukin (IL)-2 (P<0.001) impaired the release of sCD30 during allostimulation but did not alter the levels of ADAM10 and ADAM17/TACE. CD30 expression was modulated in dialysis patients in a similar way as in healthy controls.
  
  
  CONCLUSIONS
  Allostimulation results in the up-regulation of the T-cell activation marker CD30 on CD4 as well as CD8 memory T cells and increased release of sCD30 from these cells in an IFN-γ- and IL-2-dependent manner. These results may explain clinical findings on the suitability of sCD30 and IFN-γ- and IL-2-producing T cells for immune monitoring of kidney transplant recipients before and after transplantation.
authors.affiliation: Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Sonia Y
authors.initials: SY
authors.lastname: Velásquez
authors.forename: Luis F
authors.initials: LF
authors.lastname: García
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
authors.forename: Cristiam M
authors.initials: CM
authors.lastname: Alvarez
authors.forename: Caner
authors.initials: C
authors.lastname: Süsal
mesh_terms: D051722:ADAM Proteins / Q000276:immunology; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D000328:Adult; D053829:Amyloid Precursor Protein Secretases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D017730:Ki-1 Antigen / Q000097:blood / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D012995:Solubility; D015854:Up-Regulation / Q000276:immunology
chemical_list: C508594:IL2 protein, human; D007376:Interleukin-2; D007519:Isoantigens; D017730:Ki-1 Antigen; D008565:Membrane Proteins; D007371:Interferon-gamma; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human