Polyfunctional cytomegalovirus-specific CD4+ and pp65 CD8+ T cells protect against high-level replication after liver transplantation.
To determine whether polyfunctional CD4+ T-cell responses coupled with CD8+ T-cell responses against human cytomegalovirus (HCMV) are key to the control of HCMV replication we prospectively analyzed 29 liver transplant recipients for CD4+ T-cell responses against soluble HCMV antigen, pp65 and IE1 proteins, CD8+ T-cell responses against pp65 and IE1 proteins and a range of T helper (Th) 1 and Th2 cytokines. Eleven patients (38%) developed HCMV DNAemia at a median of 21 days post-liver transplantation (range 17-31 days). There was a significantly lower frequency and absolute number of total HCMV CD4+ T cells producing IFNgamma, IFNgamma+IL2 and IL2 and pp65-CD8+ T cells producing IFNgamma in patients with DNAemia. The quantities of Th1 and Th2 cytokines present during the first 20 days posttransplant were not predictive of DNAemia. Cut-off levels during the first 20 days posttransplant of 0.1% of lysate stimulated CD4+ T cells producing IL2, and pp65-CD8+ T cells producing IFNgamma above 0.4% had positive and negative predictive values for DNAemia of 54% and 100% and 50% and 92%, respectively. Measuring polyfunctional CD4+ T cells against HCMV early posttransplant may allow targeted intervention to minimize the occurrence and acute and long-term consequences of HCMV replication.
Department of Infection, Royal Free and University College Medical School, London, UK.
G
G
Nebbia
F M
FM
Mattes
C
C
Smith
E
E
Hainsworth
J
J
Kopycinski
A
A
Burroughs
P D
PD
Griffiths
P
P
Klenerman
V C
VC
Emery
D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D003587:Cytomegalovirus / Q000502:physiology*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D016014:Linear Models; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000502:physiology*; D011446:Prospective Studies; D012372:ROC Curve; D014763:Viral Matrix Proteins / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
D000956:Antigens, Viral; D004279:DNA, Viral; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D007376:Interleukin-2; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma