Abstract
Cytomegalovirus (CMV) is the most common viral infection in hematopoietic cell transplantation (HCT) recipients. We performed deep phenotyping of CMV-specific T cells to predict CMV outcomes following allogeneic HCT. By using 13-color flow cytometry, we studied ex vivo CD8
T-cell cytokine production in response to CMV-pp65 peptides in 3 clinically distinct subgroups of CMV-seropositive HCT patients: (1)
(n = 19): did not have evidence of CMV DNAemia on surveillance testing; (2)
(n = 16): spontaneously resolved low-grade CMV DNAemia without antiviral therapy; and (3)
(NC; n = 21): experienced clinically significant CMV. Two CMV-specific CD8
T-cell functional subsets were strongly associated with risk of CMV: (i) the
(NPS; IL-2
IFN-γ
TNF-α
MIP-1β
), found at increased levels among NC; and (ii) the
(PS; IL-2
IFN-γ
TNF-α
MIP-1β
) found at low levels among NC. High levels of the NPS and low levels of PS were associated with an increased 100-day cumulative incidence of clinically significant CMV infection (35% vs 5%;
= .02; and 40% vs 12%;
= .05, respectively). The highest predictive value was observed when these signatures were combined into a composite biomarker consisting of low levels of the PS and high levels of the NPS (67% vs 10%;
< .001). After adjusting for steroid use or donor type, this composite biomarker remained associated with a fivefold increase in the risk of clinically significant CMV infection. CMV-specific CD8
T-cell cytokine signatures with robust predictive value for risk of CMV reactivation should prove useful in guiding clinical decision making in HCT recipients.
