title: Proliferative alloresponse of T-cytotoxic cells identifies rejection-prone children with steroid-free liver transplantation.
abstract: Donor-induced and third-party-induced proliferation of T-helper and T-cytotoxic (Tc) cells and their naïve and memory subsets was evaluated simultaneously in single blood samples from 77 children who received steroid-free liver transplantation (LTx) after induction with rabbit anti-human thymocyte globulin. Proliferation was measured by dilution of the intravital dye carboxyfluorescein succinimidyl ester (CFSE) in a 3- to 4-day mixed lymphocyte response coculture. The ratio of donor/third-party-induced proliferated (CFSE(low)) T-cells was reported as the immunoreactivity index (IR) for each subset. Rejectors were defined as those who experienced biopsy-proven acute cellular rejection within 60 days of the assay. IR > 1 signified increased risk of rejection, and IR < 1 implied decreased risk. Demographics for 32 rejectors and 45 nonrejectors were similar. Proliferated CFSE(low) T-cells and subsets were significantly higher among rejectors compared with nonrejectors. In 33 of 77 randomly selected children, logistic regression, leave-one-out cross-validation, and receiver operating characteristic analyses showed that the IR of Tc cells was best associated with biopsy-proven rejection (sensitivity > 75%, specificity > 88%). Sensitivity and specificity were replicated in the remaining 44 children who composed the validation cohort. IR of CFSE(low) Tc cells correlated significantly with IR of proinflammatory, allospecific CD154+ Tc cells (r = 0.664, P = 0.0005) and inversely with IR of allospecific, anti-inflammatory, cytotoxic T lymphocyte antigen 4-positive Tc cells (r = -0.630, P = 0.007). In conclusion, proliferative alloresponses of Tc cells can identify rejection-prone children receiving LTx. Liver Transpl 15:978-985, 2009. (c) 2009 AASLD.
authors.affiliation: Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Chethan
authors.initials: C
authors.lastname: Ashokkumar
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.forename: Ankit
authors.initials: A
authors.lastname: Gupta
authors.forename: Brandon W
authors.initials: BW
authors.lastname: Higgs
authors.forename: Tamara
authors.initials: T
authors.lastname: Fazzolare
authors.forename: Lisa
authors.initials: L
authors.lastname: Remaley
authors.forename: George
authors.initials: G
authors.lastname: Mazariegos
authors.forename: Kyle
authors.initials: K
authors.lastname: Soltys
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Bond
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sindhi
mesh_terms: D001706:Biopsy; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005452:Fluoresceins / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D006084:Graft Rejection; D006801:Humans; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D012306:Risk; D013256:Steroids / Q000378:metabolism*; D013388:Succinimides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D005452:Fluoresceins; D005456:Fluorescent Dyes; D013256:Steroids; D013388:Succinimides