Approximately 70% of EBV asymptomatic pediatric heart transplant (HTx) recipients carry chronic EBV loads in peripheral blood. These EBV loads may occur due to impaired EBV-specific CD8⁺ T cell surveillance and/or increased EBV reactivation. Our previous results showed that occasionally, chronic EBV load carriers display circulating IL-21R⁺CXCR5⁺CD8⁺ EBV-lytic specific T cells, suggesting their recent EBV TCR-triggered activated status, their responsiveness to IL-21 and their potential to migrate to B cell follicles of the tonsils to interact with EBV-infected B cells. IL-21 is critical for driving CXCR5 expression, for viral control during chronic infections, but also for B cell differentiation that may allow EBV reactivation. Here we hypothesize that circulating IL-21R⁺CXCR5⁺CD8⁺ EBV-lytic specific T cells are generated due to increased IL-21 production by CD4⁺ T cells that coincides with EBV reactivation. To address this, we measured IL-21 production by flow cytometry, and set up RT-PCR to amplify ZEBRA on PBMC isolated from pediatric HTx patients with (n=4) or without (n=8) circulating IL-21R⁺CXCR5⁺CD8⁺ EBV-lytic T cells. Our results identified significant IL-21 production by peripheral blood CD4⁺ T cells from patients that display circulating IL-21R⁺CXCR5⁺CD8⁺ EBV-lytic specific T cells as compared to negative patients (11±5% vs 2±1% p<0.001). In addition 2 out of 4 patients with IL-21R⁺CXCR5⁺CD8⁺ EBV-lytic specific T cells present EBV lytic (ZEBRA) transcripts, while none of the negative patients were ZEBRA positive. These results suggest that EBV reactivation is not a continuous event for patients who carry EBV loads. However, IL-21 production and circulating IL-21R⁺CXCR5⁺CD8⁺ EBV-lytic specific T cells can indicate recent EBV reactivation. Monitoring these parameters in the clinic may help identify patients with frequent EBV reactivation, at risk of developing dangerous high EBV loads and EBV complications.

« Back to 2015 American Transplant Congress