Allospecific CD154+ T-cytotoxic memory cells identify recipients experiencing acute cellular rejection after renal transplantation

Background.: The novel, recently described allo (antigen)-specific CD154+T cells were evaluated for their association with acute cellular rejection (ACR) in 43 adult renal transplant recipients receiving steroid-free tacrolimus after alemtuzumab induction. Methods.: Single blood samples corresponding to "for cause" allograft biopsies were assayed for CD154+naive or memory T-helper or T-cytotoxic cells in 16-hr mixed leukocyte reaction. Results.: Intra- and interassay variation was less than 10% for a variety of conditions. In logistic regression, leave-one-out cross-validation, and receiver-operating characteristic analyses, the rejection-risk threshold of allospecific CD154+T-cytotoxic memory cells (TcMs) associated best with biopsy-proven ACR with a sensitivity/specificity of 88% in 32 of 43 subjects. Sensitivity/ specificity of 100%/88% was replicated in blinded prediction in the remaining 11 subjects. Allospecific CD154+TcM correlated inversely with CTLA4+TcM (Spearman r=-0.358, P=0.029) and increased significantly with increasing histological severity of ACR (P=2.99E-05, Kruskall-Wallis). Conclusions.: The strong association between ACR and allospecific CD154+TcM may be useful in minimizing protocol biopsies among recipients at reduced rejection risk.