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.
Department of Virology, Royal Free and University College Medical School, London, United Kingdom.
A F
AF
Hassan-Walker
A L
AL
Vargas Cuero
F M
FM
Mattes
P
P
Klenerman
F
F
Lechner
A K
AK
Burroughs
P D
PD
Griffiths
R E
RE
Phillips
V C
VC
Emery
D000293:Adolescent; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016031:Liver Transplantation / Q000276:immunology*; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016559:Tacrolimus / Q000494:pharmacology*; D013997:Time Factors; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000276:immunology
D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma; D016559:Tacrolimus