Ashokkumar C, Green M, Soltys K, Michaels M, Mazariegos G, Reyes-Mugica M, Higgs BW, Spishock B, Zaccagnini M, Sethi P, Rzempoluch A, Kepler A, Kachmar P, Remaley L, Winnier J, Jones K, Moir K, Fazzolare T, Jenkins K, Hartle T, Falik R, Ningappa M, Bond G, Khanna A, Ganoza A, Sun Q, Sindhi R. CD154-expressing CMV-specific T cells associate with freedom from DNAemia and may be protective in seronegative recipients after liver or intestine transplantation. Pediatr Transplant. 2019 Oct 27:e13601. doi: 10.1111/petr.13601. PubMed PMID: 31657119.
ABSTRACT
Cell-mediated immunity to CMV, if known, could improve antiviral drug therapy in at-risk children and young adults with LT and IT. Host immunity has been measured with CMV-specific T cells, which express IFNγ, but not those which express CD154, a possible substitute for IFNγ. CMV-specific CD154+ T cells and their subsets were measured with flow cytometry after stimulating PBL from recipient blood samples with an overlapping peptide mix of CMV-pp65 antigen for up to 6 hours. CMV-specific CD154+ T cells co-expressed IFNγ in PBL from three healthy adults and averaged 3.8% (95% CI 3.2%-4.4%) in 40 healthy adults. CMV-specific T cells were significantly lower in 19 CMV DNAemic LT or IT recipients, compared with 126 non-DNAemic recipients, 1.3% (95% CI 0.8-1.7) vs 4.1 (95% CI 3.6-4.6, P < .001). All T-cell subsets demonstrated similar between-group differences. In logistic regression analysis of 46 training set samples, 12 with DNAemia, all obtained between days 0 and 60 from transplant, CMV-specific T-cell frequencies ‰¥1.7% predicted freedom from DNAemia with NPV of 93%. Sensitivity, specificity, and PPV were 83%, 74%, and 53%, respectively. Test performance was replicated in 99 validation samples. In 32 of 46 training set samples, all from seronegative recipients, one of 19 recipients with CMV-specific T-cell frequencies ‰¥1.7% experienced DNAemia, compared with 8 of 13 recipients with frequencies <1.7% (P = .001). CMV-specific CD154+ T cells are associated with freedom from DNAemia after LT and IT. Among seronegative recipients, CMV-specific T cells may protect against the development of CMV DNAemia.
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