Antigen-specific T cells, which express CD154 rapidly, but remain untested in alloimmunity, were measured with flow cytometry in 16-h MLR of 58 identicallyimmunosuppressed children with liver transplantation (LTx), to identify Rejectors (who had experienced biopsy-proven rejection within 60 days posttransplantation). Thirty-one children were sampled once, cross-sectionally. Twenty-seven children were sampled longitudinally, pre-LTx, and at 1-60 and 61-200 days after LTx. Results were correlated with proliferative alloresponses measured by CFSE-dye dilution (n = 23), and CTLA4, a negative T-cell costimulator, which antagonizes CD154-mediated effects (n = 31). In cross-sectional observations, logistic regression and leave-one-out cross-validation identified donorspecific, CD154 + T-cytotoxic (Tc)-memory cells as best associated with rejection outcomes. In the longitudinal cohort, (1) the association between CD154 + Tcmemory cells and rejection outcomes was replicated with sensitivity/specificity 92.3%/84.6% for observations at 1-60 days, and (2)

Background/Aims-Limited access to large samples and independent replication cohorts precludes genome-wide association (GWA) studies of rare but complex traits. To localize candidate genes with family-based GWA, a novel exploratory analysis was first tested on 1,774 major histocompatibility complex single nucleotide polymorphisms (SNPs) in 240 DNA samples from 80 children with primary liver transplantation (LTx), and their biological parents.

Multiple measurements of lymphocyte subsets in 91 children treated with steroid-free Tacrolimus, and rabbit anti-human thymocyte globulin induction demonstrate early reconstitution of T-cytotoxic cells, and gradual reconstitution of all other subsets, which is complete after 1 year. Rejection-prone children demonstrate significantly higher counts of lymphocytes and all subsets prior to liver transplantation, and may exemplify one basis for enhanced baseline immunocompetence.