title: Activated HLA class I-reactive cytotoxic T lymphocytes associated with a positive historical crossmatch predict early graft failure.
abstract: BACKGROUND
  Preexisting alloantibodies against the mismatched HLA class I antigens of the donor, when present in current sera, are believed to be detrimental for kidney graft survival. The relevance of a positive crossmatch with historical sera only is still a matter of debate. Previous studies showed a correlation between the presence of alloantibodies and the presence of alloactivated cytotoxic T lymphocytes (CTLs). We wondered whether the persistence of activated CTLs might explain the poor results in a proportion of patients with a historical positive crossmatch.
  
  
  METHODS
  We tested 10 sensitized patients to determine whether activated CTLs persist when the antibodies disappear. Limiting dilution assays were performed in the presence and absence of cyclosporine (CsA) to distinguish between activated (primed) (CsA resistant) and naive (CsA sensitive) CTLs. To test the clinical relevance of the persisting CTLs, eight sensitized patients, who underwent a kidney transplantation across a positive historical crossmatch, were retrospectively tested for the presence or absence of activated donor-specific CTLs at the day of transplantation.
  
  
  RESULTS
  In the first group, four patients had CsA-sensitive CTLs, three patients had CsA-resistant CTLs, and three other patients had CsA-sensitive CTLs for a particular HLA antigen and CsA-resistant CTLs for another HLA antigen. In the transplant group, four patients with CsA-sensitive CTLs at the day of transplantation were found to have a good graft function. In the other four patients, the presence of CsA-resistant donor-specific CTLs was associated with rejection and early graft loss.
  
  
  CONCLUSIONS
  The present study suggests that determining the activation state of CTLs specific for the HLA mismatch against which antibodies were present in historical sera, may be relevant to transplant outcome in patients who undergo transplantation across a positive historical crossmatch.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Building 1 E3-Q, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. C.A.van_Kampen@lumc.nl
authors.forename: Corine A
authors.initials: CA
authors.lastname: van Kampen
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Minke F J
authors.initials: MF
authors.lastname: Versteeg-van der Voort Maarschalk
authors.forename: Andries J
authors.initials: AJ
authors.lastname: Hoitsma
authors.forename: Wil A
authors.initials: WA
authors.lastname: Allebes
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D011237:Predictive Value of Tests; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry* / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies; D007519:Isoantigens