Activated virus-specific T cells are early indicators of anti-CMV immune reactions in liver transplant patients

Background & Aims: Cytomegalovirus (CMV) infection represents the most common infectious complication after liver transplantation. Because CMV-associated complications in liver transplantation patients are often liver-restricted and clinically unrecognized, diagnosis of early infection or reactivation is still very difficult. Because cytotoxic T cells (CTLs) are crucial for the immune control of CMV, analysis of virus-specific CTLs could contribute to diagnosis and management of CMV infection. Methods: Major histocompatibility complex class I tetramers and intracellular cytokine staining were used to determine frequencies and phenotypes of peripheral blood CMV/pp65-specific CD8⁺ T cells in HLA-A2, -B7, and -B35 positive liver transplantation patients and in healthy individuals. Results: After liver transplantation (6-33 months after liver transplantation), frequencies of CMV-specific T cells were significantly elevated compared with healthy individuals. In contrast to immunoglobulin (Ig) M-negative patients and healthy blood donors, patients with increasing CMV IgM titers or IgG seroconversion had high percentages of activated (CD38^high) CMV-specific T cells. In recently transplanted patients, activation of CMV-specific T cells was associated with increased transaminases and histopathological abnormalities in the absence of positive CMV-polymerase chain reaction results from peripheral blood. Conclusions: These data indicate that T-cell analysis based on MHC tetramer staining may 'be a valuable parameter in the early diagnosis of CMV-induced, liver-restricted complications after liver transplantation.