Direct visualization and quantitation of cytomegalovirus-specific CD8+ cytotoxic T-lymphocytes in liver transplant patients.
BACKGROUND
CMV infection remains a significant clinical problem in the context of LT. Changes in the magnitude of the CMV-specific CTL response after LT have not previously been assessed but may be important in determining the outcome of CMV infection.


METHODS
We used a fluorescent HLA-B*0702-CMV peptide tetrameric complex to directly visualize and quantitate CMV-specific CD8+ CTL both in immunosuppressed patients after LT and in immunocompetent controls.


RESULTS
CMV-specific CD8+ CTL, at a frequency ranging from 0.1 to 5.8% of CD8+, were detected in the peripheral blood of 22 of 25 B*0702, CMV immunoglobulin G seropositive individuals, with no difference observed between immunocompetent controls and patients >3 years after LT. In CMV seropositive LT recipients who did not have symptomatic CMV infection during the first 3 months after LT, CMV-specific CD8+ CTL magnitude initially decreased, then increased up to 5 times higher than pre-LT levels within 3 months. Two CMV seronegative recipients of seropositive donors had symptomatic CMV infection in association with high viral load. In both patients, no CD8+ CTL response was detected before the onset of symptoms, and a reduction in viral load was observed during antiviral therapy. However, polymerase chain reaction negativity was achieved only when a demonstrable CMV-specific CD8+ CTL response was generated. Responses were never observed in asymptomatic CMV seronegative patients.


CONCLUSIONS
We suggest that the generation of CMV-specific CD8+ CTL may be driven by, and seems to coincide with the suppression of, viral reactivation. Direct monitoring of CMV-specific CD8+ CTL using an HLA-peptide tetramer may prove to be of value in the management of patients after LT.
Singhal
S
S
Liver Research Laboratories, Queen Elizabeth Hospital, Birmingham, England. s.singhal@bham.ac.uk
Shaw
J C
JC
Ainsworth
J
J
Hathaway
M
M
Gillespie
G M
GM
Paris
H
H
Ward
K
K
Pillay
D
D
Moss
P A
PA
Mutimer
D J
DJ
D001769:Blood / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000821:virology; D006801:Humans; D007121:Immunocompetence; D007075:Immunoglobulin M / Q000097:blood; D016031:Liver Transplantation / Q000276:immunology*; D008137:Longitudinal Studies; D011184:Postoperative Period; D011446:Prospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D019562:Viral Load
D007075:Immunoglobulin M