Cytomegalovirus-specific CD154-expressing T Cells are Present Before Transplantation in Cytomegalovirus-seronegative Recipients and Predict Early Cytomegalovirus DNAemia

Background. Cytomegalovirus (CMV) antiviral drugs can cause side effects and promote the emergence of drug-resistance after transplantation. T cell–mediated immunity to CMV (CMI) can be used to limit and optimize the duration of antiviral therapy. However, interferon-gamma release assays show varying rates of CMI in CMV-seronegative recipients (R – ), who are at the highest risk of CMV infection with CMV-seropositive donors (D + ). Here, we characterize CMI with CMV-specific T cells that express CD154 in R – liver transplant and intestine transplant recipients. Methods. Pretransplant blood leukocyte samples from 42 R – recipients were stimulated with a 15-mer overlapping peptide mixture representing the pp65 CMV antigen. CMI was measured by flow cytometry with CMV-specific CD154 + T-cell frequencies. Results. Recipients, median age (range) 3.3 (0.4–36.5 y), included 39 liver transplant and 3 intestine transplant. CMV serostatus was D + /R – in 21, and D – /R – in 21. Protective CMI levels of >1.7% previously established in 142 liver or intestine recipients were observed in 25 of 42 total R – recipients (60%), including 11 of 21 D + /R – (52%) and 14 of 21 D – /R – (67%) participants. CMV DNAemia was observed in the first 60 d after transplantation in 10 of 42 (24%) R – recipients, including 8 of 17 with CMI <1.7% and 2 of 25 with CMI >1.7%. Adjusted for D + /R – , CMI<1.7% was independently associated with a higher risk of DNAemia (hazard ratio 6.04 [1.2-29.4], P = 0.026). Conclusions. CMV-specific T cells that express CD154 demonstrate protective levels of CMI in half of all seronegative recipients and can be used to optimize antiviral prophylaxis across all risk categories.