REPERTOIRE, MEMORY SUBSETS, AND FUNCTION OF EBV-SPECIFIC CD8+T CELLS IN PERIPHERAL BLOOD FROM STABLE SOLID ORGAN TRANSPLANT PATIENTS.

1.5
#69-OR
REPERTOIRE, MEMORY SUBSETS, AND FUNCTION OF EBV-SPECIFIC CD8+T CELLS IN PERIPHERAL BLOOD FROM STABLE SOLID ORGAN TRANSPLANT PATIENTS.
Camila Macedo MD , Iulia Popescu PhD , Alison Logar BS , Kareem Abu-Elmagd MD , Ron Shapiro MD , Jorge Reyes MD , Adriana Zeevi PhD , John Fung MD and Diana Metes MD . Pittsburgh PA, Thomas E. Starzl Transplantation Institute, 15213, Surgery .

Epstein-Barr virus (EBV), a B cell lymphotropic herpes virus, establishes a life-long persistence in humans. Memory CD8 T cell responses against viral antigens control subsequent episodes of viral reactivation. Consequently, solid organ transplant (SOTx) patients display an impaired protective T cell surveillance due to chronic immunosuppression (IS), and therefore are at increased risk to develop Post Transplant Lymphoproliferative Disorders (PTLD). Here we have assessed the EBV-specific CD8 T cells isolated from IS SOTx patients and healthy individuals. HLA-A0201 tetramer folded with peptides derived from the lytic cycle (BMLF1), and from the latent cycle (LMP2 and EBNA3A) Ag were used in flow cytometry in peripheral blood from 15 EBV+ stable IS SOTx patients and 9 healthy individuals. In addition, we characterized the central and effectory memory subsets of the EBV-specific CD8 T cells. The functional ability of these cells to produce IFN-γ was analyzed by ELISPOT assay using the same EBV-specific peptides. Although, IS SOTx patients had a decreased "central memory" pool in favor of " effector memory”, the EBV-specific repertoire was comparable to the controls. Interestingly, patients had a higher frequency of EBV-specific CD8 T cells suggesting that clone proliferation was preserved. However, IFN-γ release after EBV-stimulation was lower in patients, with significantly lower values in response to LMP2 stimulation (p<0.05). Results suggest that IS therapy impairs the EBV-specific CD8 to produce IFN-g in response to EBV-specific stimulation, but this deficit seems to be overcome in stable SOTx patients by an increase in the frequency of EBV-specific CD8 T cells.