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. © 2009 AASLD.