Activated virus-specific T cells are early indicators of anti-CMV immune reactions in liver transplant patients.
OBJECTIVE
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.
Benz
Christine
C
Department of Gastroenterology, Institute of Medical Microbiology, Immunology, and Hygiene, University of Cologne, Cologne, Germany.
Utermöhlen
Olaf
O
Wulf
Anna
A
Villmow
Brigitte
B
Dries
Volker
V
Goeser
Tobias
T
Koszinowski
Ulrich
U
Busch
Dirk H
DH
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D003587:Cytomegalovirus / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D016031:Liver Transplantation; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000032:analysis; D010750:Phosphoproteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D014775:Virus Activation
D015703:Antigens, CD; D000943:Antigens, Differentiation; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1