Co-expression of PD1+ and HLA-DR+ in CD8+ T cells is increased in tonsils of children with EBV primary and persistent infection

María Eugenia Amarillo¹Karen Lindl¹Veronica Lapido¹Ignacio E Rojas Campión²Maria Soledad Collado²Johanna Speratti³Andrea Valerio³Plácida Baz²ELENA DE MATTEO¹Luis Ariel Billordo²Paola Chabay^1*

• ¹CONICET Instituto Multidisciplinario de Investigación en Patologías Pediátricas (IMIPP), Buenos Aires, Argentina
• ²Institute of Immunology, Genetics and Metabolism (INIGEM), Clinical Hospital 'José de San Martín', UBA-CONICET, Buenos Aires, Argentina
• ³Otorhinolaryngology Division, Ricardo Gutierrez Children Hospital, Buenos Aires, Argentina

Epstein-Barr virus (EBV) infects B lymphocytes and establishes lifelong persistence in the B cells. While systemic T cell responses have been well characterized, the local immune response at the site of viral entry in children from undeveloped countries remains poorly understood. Tonsillar CD4 and CD8 T cells in 32 pediatric patients undergoing tonsillectomy were classified as primary infected (PI), EBV carriers (EC) and non-infected children by serology. T cell subsets were assessed by flow cytometry, while LMP1 and EBNA2 viral proteins were evaluated by immunohistochemistry. A higher percentage of activated HLA-DR+ CD8 T cells in PI patients was demonstrated. Notably, PD-1 expression was increased in both PI and EC, in particular in activated HLA-DR+ CD8 T cells. Positive correlations of EBNA2 with follicular helper T cells and Th1 cells, as well as negative correlation between EBNA2 and activated CD8 T cells was observed. These findings suggest that, during asymptomatic primary infection by EBV, activated CD8 T cells are observed, but they may be cells that may exhibit features of exhaustion, which probably explains the absence of symptoms. PD-1 expression in CD8 T cells remains in EC. Additionally, Tfh, Th1 and CD8 T cells may influence the expression of EBNA2 and LMP1 latent viral antigens in tonsils.