Kinetics of cytomegalovirus (CMV) pp65 and IE-1-specific IFNgamma CD8+ and CD4+ T cells during episodes of viral DNAemia in allogeneic stem cell transplant recipients: potential implications for the management of active CMV infection.
The dynamics of CMV pp65 and IE-1-specific IFNgamma-producing CD8(+) (IFNgamma CD8(+)) and CD4(+) (IFNgamma CD4(+)) T cells and CMV DNAemia were assessed in 19 pre-emptively treated episodes of active CMV infection. Peripheral counts of IFNgamma CD8(+) and IFNgamma CD4(+) T cells inversely correlated with CMV DNAemia levels (P = <0.001 and P = 0.003, respectively). A threshold value of 1.3 cells/microl predicting CMV DNAemia clearance was established for IFNgamma CD8(+) T cells (PPV, 100%; NPV, 93%) and for IFNgamma CD4(+) T cells (PPV, 100%; NPV, 75%). Undetectable T-cell responses were usually observed at the time of initiation of pre-emptive therapy. Either a rapid (within 7 days) or a delayed (median 31 days) expansion of both T-cell populations concomitant with CMV DNAemia clearance was observed in 5 and 8 episodes, respectively. An inconsistent or a lack of expansion of both T-cell subsets was related to a persistent CMV DNAemia. Robust and maintained CMV-specific T-cell responses after CMV DNAemia clearance and cessation of antiviral therapy were associated with a null incidence of relapsing infections at least during the following month. Data obtained in the present study may be helpful in the design of therapeutic strategies for the management of active CMV infections in the allo-SCT recipient.
Microbiology Service, Clinic University Hospital, Valencia, Spain.
Nuria
N
Tormo
Carlos
C
Solano
Isabel
I
Benet
José
J
Nieto
Rafael
R
de la Cámara
Ana
A
Garcia-Noblejas
María Angeles
MA
Clari
Marifina
M
Chilet
Javier
J
López
Juan Carlos
JC
Hernández-Boluda
María José
MJ
Remigia
David
D
Navarro
D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D023381:Endpoint Determination / Q000379:methods; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood*; D033581:Stem Cell Transplantation; D037182:T-Cell Antigen Receptor Specificity; D014184:Transplantation, Homologous; D014763:Viral Matrix Proteins / Q000097:blood*
D004279:DNA, Viral; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma