title: The frequency of interferon-gproducing cells reflects alloreactivity against minor histocompatibility antigens.
abstract: BACKGROUND
  In human leukocyte antigen (HLA)-identical living-related renal transplant recipients, no donor-specific alloreactivity can be detected in regular tests (mixed lymphocyte culture, helper T-lymphocyte precursor frequencies, cytotoxic T-lymphocyte precursor frequencies) to identify patients responding to minor histocompatibility antigens (mHag). We questioned whether a more sensitive method like the Elispot-assay could be more appropriate.
  
  
  RESULTS
  Peripheral blood mononuclear cells (PBMC) from 16 HLA-identical living-related kidney transplant patients 3 months (range, 2 weeks to 5 months) after transplantation were tested for the frequency of interferon (IFN)-gamma producing cells by the Elispot-assay. PBMC from the recipient were stimulated with irradiated donor PBMC and corrected for backward stimulation. Donor-specific IFN-gamma producing cells (pc) in the range of 5 to 115 per million PBMC (median, 30 per million PBMC) were found. To evaluate the frequency of spot forming cells in time, PBMC from six patients who received an HLA-identical renal transplant were stimulated with irradiated donor PBMC before, approximately 3 months after, and 12 months after transplantation. Four patients who received an HLA-mismatched living-related kidney served as positive control. In the HLA-identical group, frequencies in the range of 0 to 10 IFN-gamma pc per million PBMC were found before transplantation, 0 to 30 per million PBMC 3 months after transplantation, and 0 to 45 per million PBMC 12 months after transplantation. In the HLA-mismatched group, significantly higher numbers were found: 10 to 480 IFN-gamma pc per million PBMC before, 20 to 360 per million PBMC at 3 months, and 30 to 590 per million PBMC 12 months after transplantation.
  
  
  CONCLUSIONS
  Under immunosuppressive therapy, IFN-gamma pc specific for donor mHag can be found after HLA-identical living-related renal transplantation.
authors.affiliation: Department of Internal Medicine-Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands. n.vanbesouw@erasmusmc.nl.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: van Besouw
authors.forename: Lenard M B
authors.initials: LM
authors.lastname: Vaessen
authors.forename: Joke M
authors.initials: JM
authors.lastname: Zuijderwijk
authors.forename: Marleen
authors.initials: M
authors.lastname: van Vliet
authors.forename: Jan N M
authors.initials: JN
authors.lastname: IJzermans
authors.forename: Peter H
authors.initials: PH
authors.lastname: van Der Meide
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
mesh_terms: D001787:Blood Group Incompatibility; D005260:Female; D006648:Histocompatibility; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007518:Isoantibodies / Q000032:analysis*; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D009000:Monocytes / Q000378:metabolism*; D011184:Postoperative Period; D013997:Time Factors
chemical_list: D007518:Isoantibodies; D015778:Minor Histocompatibility Antigens; D007371:Interferon-gamma