Transplantation direct · 2026
Cytomegalovirus-specific CD154-expressing T Cells are Present Before Transplantation in Cytomegalovirus-seronegative Recipients and Predict Early Cytomegalovirus DNAemia.
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Remaley Lisa, Soltys Kyle, Fazzolare Tamara, Ningappa Mylarappa, Green Michael, Michaels Marian, Paul Morgan, Spishock Brianna, Wilkerson Dawn, Raghu Vikram, Higgs Brandon W, Mazariegos George, Khanna Ajay, Ganoza Armando, Bond Geoffrey, Ashokkumar Chethan, Sindhi Rakesh
Аннотация
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.
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.