Background: EBV infection and post-transplant lymphoproliferative disorders (PTLD) are life-threatening complications of pediatric solid organ transplantation (Tx). Chronic high EBV viral load (HVL) carriers have a 45% risk for developing PTLD in pediatric thoracic Tx (ThoTx) recipients; However, the incidence of PTLD in abdominal Tx (AbdTx) HVL carriers is ≤ 3 %. Literature reports that chronic infections may result in T cell exhaustion, dominated by terminal progeny phenotypes (PD-1^HI/Eomes^HI with CD127^LO/T-bet^LO) paralleled by a loss of progenitor phenotypes (PD-1^INT/T-bet^HI with CD127^HI/Eomes^LO). Therefore, we hypothesized that ThoTx HVL patients prone to develop PTLD preferentially expand terminally exhausted cellular progeny, while AbdTx HVL patients remain at low risk for PTLD due to persistence of functional antiviral immune progenitors despite of high EBV pressure.

Methods: 54 whole blood samples from ThoTx and AbdTx (kidney and liver) recipients were analyzed by Flow cytometry with MHC-dextramers and markers of exhaustion staining. Tx recipients' viral load status was classified as follows: Undetectable Viral Load (UVL: no or unquantifiable EBV load), Low Viral Load (LVL: 100-16,000 EBV genomic copies/mL blood) and HVL (>16,000 EBV genomic copies/mL blood). Kruskal-Wallis H test was used across groups with p<0.05 considered significant.

Results: EBV loads from ThoTx recipients correlated directly with PD-1^HI/Eomes^HI (p<0.09) and inversely with CD127 (p<0.004) expression on EBV-specific CD8^+- T cells. Loss of T-bet occurred in all EBV ThoTx carriers. Conversely, no such correlations between EBV loads and phenotypes were observed with AbdTx recipients, where expression of PD-1 and Eomes were at low levels and were paralleled by expansion of CD127^HI/T-bet^HI EBV-specific CD8⁺ T cells in all patients.

Conclusion: Terminally exhausted EBV-specific CD8⁺ T cell progeny were only observed in HVL ThoTx patients, while AbdTx patients, including HVL carriers maintained effector progenitor phenotypes. These findings may explain in part distinct mechanisms that could concur to the significantly different outcomes of EBV complication after pediatric organ transplantation.

CITATION INFORMATION: Yamada M, Camila M, Fadakar P, Hornor K, Michaels M, Green M, Nguyen C, Feingold B, Mazariegos G, Metes D. EBV-Specific CD8⁺ T Cells from Pediatric Thoracic vs Abdominal Transplant Recipients Are Shaped Differently by the Chronic EBV Loads with Potential Impact on the Risk of PTLD. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress