*Purpose: After lung transplantation, Epstein-Barr virus (EBV) is a common opportunistic infection. The significance of EBV viremia following solid organ transplantation (SOT) remains unclear. Host immune responses to EBV after lung transplant have not been well characterized.

*Methods: We analyzed by flow cytometry frequencies of NK cells subsets and the differential expression of NKG2A and NKG2D receptors in lung transplant recipients (LTRs) without EBV-related disease (n=10), those with EBV viremia (n=5), and those with post-transplant lymphoproliferative disorder (PTLD) (n=3). We then analyzed T-cell frequencies and EBV-specific poly-functional responses after stimulation with BZFL1 (lytic) and EBNA-3B (latent)-derived peptides in LTRs without EBV-related disease (n=10), those with EBV viremia (n=5).

*Results: Interestingly, LTRs with PTLD demonstrated high frequencies of CD56^dimCD16^neg NK cells (Fig. 1B) as described in patients with infectious mononucleosis. Frequency of more differentiated CD56^dimCD16^pos NK cells were significantly decreased in both cohorts of LTRs with EBV viremia and PTLD (Fig. 1C). The analysis of differential expression of NKG2A in NK cell subsets demonstrated a significant increase of NKG2A expression in CD56^dimCD16^neg NK cells in LTRs with EBV viremia (Fig. 1E). We then study T cells frequencies and responses. We noted that LTRs with EBV viremia had a significantly decreased CD4/CD8 ratio compared to healthy donors and LTRs without EBV-disease. We noted little difference in CD4+T cells responses (Fig.2A-B), while in the CD8+ population a trend was observed in the CD107, IFN–γ, and TNFα response to BZLF1 (Fig.2 C-D). Staphylococcal enterotoxin B (SEB) induced responses broadly indicating that T cells maintained activation potential.

*Conclusions: These findings suggest that EBV viremia in LTRs is associated with perturbation of innate and adaptive immune responses. The presence of a less cytotoxic NK cell subset and possibly the loss of poly-functional T cell responses might be associated with development of EBV viremia and subsequently malignant transformation to PTLD.

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