Characterization of Epstein Barr virus (EBV) microenvironment composition in pediatric asymptomatic carriers

VISTAROP A; COHEN, M; FUAD H; DE MATTEO E; PRECIADO MV; PAOLA ANDREA CHABAY

Zurich

Congreso; 17th International Symposium on EBV and Associated Diseases; 2016

EBV association

EBV primary infection in Argentina is subclinical at young age. Our aim was to analyze tonsil microenvironment around EBV+ cells and to compare it with EBV- zone. LMP1 expression by immunohistochemistry (IHC) discriminated EBV+ and ?zones in 11 tonsil biopsies from pediatric carriers (2-5years). We defined 5 tissue regions: SUBEPITHELIAL REGION (SR) comprising Intra Superficial Epithelium (ISE) and Crypt; INTERFOLLICULAR (IF) and GERMINAL CENTER (GC) (Primary (PGC) and Secondary (SGC)). IHC was performed on serial sections to detect CD4, CD8, Foxp3 and GrzB. Positive cells/total cells were counted. The number of SR CD8+cells was higher in EBV+ than EBV- zones (p=0.02,M-Wtest). Patients with EBV+ cells at SR, showed a statistically significant direct correlation between CD8+cells and age (r=0.6;p=0.04,Spearman correlation). These differences increased when the Crypt was exclusively analyzed (p=0.02,M-Wtest and r=0.8;p=0.004,Spearman correlation).In these regions GrzB did not show statistically difference between EBV+ and - zones (p>0.05,M-Wtest). We found positive correlation between Foxp3+ and GrzB+ cells in cases with IES EBV+ cells (r=0.8;p=0.04,Spearman correlation). Significantly higher CD4+cells in SGC when compared with EBV- zone was observed (p=0.006,M-Wtest). We found that asymptomatic EBV infection in our series elicits a local CD8+T-cell response, as demonstrated by higher CD8+cells exclusively at EBV+ SR region, maybe reflecting a recruitment to control viral infection. However, cytotoxic GrzB+ effector subset was not prevalent, possibly counterbalanced by tolerogenic environment in EBV+ zone suggested by positive correlation between Foxp3+ and GrzB+ cells. CD8+cell number increased at older age, maybe as a result of matured immune system. An expansion of CD4+cells in GC might enable the transition from LIII to LII and perhaps controls transformation process as previously suggested.