CD8+ cytotoxic lymphocyte responses against cytomegalovirus after liver transplantation:: Correlation with time from transplant to receipt of tacrolimus

The effects of the immunocompromised state after liver transplantation on the frequency of cytomegalovirus-specific cytotoxic T lymphocytes (CTL) were investigated in 93 patients by using HLA class I tetrameric complexes corresponding to HLA-A*0201, HLA-B*0702, HLA-B*0801, and HLA-B*3501 refolded with peptides from the ppUL83 matrix protein. ppUL83 CTL frequencies were suppressed during the first 6 months after transplantation. Patients with >1 HLA-restricted response detected had high correlation among ppUL83 CD8(+) CTL frequencies restricted by different HLA haplotypes (Spearman's rho = .67; P < .0001). There was an inverse correlation among levels of the calcineurin inhibitor, tacrolimus, and ppUL83 CD8(+) CTL frequencies (r = -.31; P = .005), which is consistent with the presence of a large proportion (70%) of activated (CD38(+)) ppUL83 CD8+ CTL within the population of HLA class I tetramer-positive cells.