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

Abstract 

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.

GASTROENTEROLOGY 2002;122:1201-1215

Abbreviations:  CMV , cytomegalovirus, EBV , Epstein–Barr virus, FACS , fluorescence-activated cell sorter, FITC , fluorescein isothiocyanate, IFN , interferon, IL , interleukin, MHC , major histocompatibility complex, PBMC , peripheral blood mononuclear cell, PCR , polymerase chain reaction, TNF , tumor necrosis factor