Reconstitution of CMV pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T-cell responses affording protection from CMV DNAemia following allogeneic hematopoietic SCT.
Threshold levels of CMV-specific T-cell populations presumably affording protection from active CMV infection in allo-SCT recipients have been proposed, but lack extensive validation. We quantified CMV pp65 and immediate-early 1-specific IFN-γ CD8(+) and CD4(+) T cell responses at days +30, +60 and +90 after transplantation in 133 patients, and established cutoff cell levels protecting from CMV DNAemia within the first 120 days after transplantation. No patients showing IFN-γ CD8(+) or IFN-γ CD4(+) T-cell counts >1.0 and >1.2 cells/μL, respectively, developed a subsequent episode of CMV DNAemia. Initial or recurrent episodes of CMV DNAemia occurred in the face of IFN-γ T-cell levels below defined thresholds. Negative predictive values at day +30 for the IFN-γ CD8(+) and CD4(+) T-cell markers were 68.1 and 61.8%, respectively. Recipients of grafts from CMV seropositive, related or HLA-matched donors, or receiving non-myeloablative conditioning had nonsignificant tendencies to reach more frequently protective levels of both T-cell subsets at early and late (day +365) times after transplantation. The use of anti-thymocyte globulin and umbilical cord blood transplantation were associated with impaired CMV-specific T-cell reconstitution. CMV-specific IFN-γ CD8(+) and CD4(+) T-cell recovery occurred irrespective of detectable CMV DNAemia.
Microbiology Service, Department of Microbiology, Hospital Clínico Universitario, School of Medicine, Valencia, Spain.
N
N
Tormo
C
C
Solano
I
I
Benet
J
J
Nieto
R
R
de la Cámara
J
J
López
A
A
Garcia-Noblejas
B
B
Muñoz-Cobo
E
E
Costa
M A
MA
Clari
J C
JC
Hernández-Boluda
M J
MJ
Remigia
D
D
Navarro
D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000097:blood* / Q000517:prevention & control / Q000821:virology; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000096:biosynthesis*; D014184:Transplantation, Homologous / Q000009:adverse effects; D014763:Viral Matrix Proteins / Q000096:biosynthesis*; D014775:Virus Activation
D004279:DNA, Viral; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma