Background: Preliminary data suggest that measuring host cellular immunity using CMV-specific IFNg+T-cells can potentially enhance decision making about discontinuation of antiviral therapy and secondary prophylaxis with ganciclovir. Here, we assess CMV-specific T-cells, which express CD40 ligand or CD154(CD154+T-cells) **, as an alternative assessment of CMV-specific cellular immunity. Purpose: To characterize cellular immunity to CMV in children with LTx and ITx who have CMV infection, and those are not infected, independent of CMV serologic status: seropositive (CMVIgG+) or seronegative (CMVIgG-). CMV infection was defined as >100 CMV copies/ml whole blood by PCR. Methods: Peripheral blood leukocytes from single blood samples obtained after transplantatoin were stimulated with an overlapping peptide mix of CMV-pp65 antigen and CD154+T-cell frequencies measured with flow cytometry in 39 children with LTx or ITx. Results: Distribution of demographics was median age 8 years (range 1-27), Male: Female gender 18:21, Caucasian: non-caucasian race 31: 8, LTx: ITx 29:10. Samples were obtained at 1606 days (14-6134) after transplantation. Distribution of CD154+T-cells among eight infected and 31 uninfected children was (mean±SD) 1.1±0.6% and 4.4±1.8%, respectively. In logistic regression analysis, which also incorporated age, gender, race, and time of sampling after transplantation, CD154+T-cells ≤ 1.78% were present in 7/8 children with CMV infection and 1/31 uninfected children. Sensitivity, specificity, positive and negative predictive values were 87.5% (95% CI-47-100), 96.7% (95% CI-83-100), 87.5% (95% CI-47-100) and 96.7% (95% CI-83-100), respectively. Among uninfected children, CD154+T-cells were significantly lower among seronegative (n=4) compared with seropositive (n=27) children (1.98 vs 4.76, p=0.017, respectively). No such differences were observed among infected children (1.03 vs 1.35%, p=NS, respectively) whether they were seropositive (n=6) or seronegative (n=2).

Conclusions: CMV-specific CD154+T-cells identify pediatric LTx and ITx recipients at risk for post-transplant CMV infection with clinically acceptable sensitivity, and require validation in a larger cohort.

**Patent application: US20060275752, Assignee University of Pittsburgh, Licensee Plexision, Inc, Pittsburgh.

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