Local CD4+Foxp3+ T cell response in tonsil of children with EBV infection

AMARILLO ME; MOYANO, A; FERRESSINI GERPE, NM; DE MATTEO E; PRECIADO MV; PAOLA ANDREA CHABAY

Congreso; 46th 46th International Herpesvirus Workshop; 2022

Our aim was to study CD4+ T cells in pediatric Epstein Barr Virus (EBV) infection to clarify viral contribution to lymphomagenesis. We studied 18 patients undergoing tolsillectomy. EBV infection status was defined by serology. Immunohistochemistry (IHC) was performed for IL-10 expression and for LMP-1 and EBNA2 viral proteins. Results were expressed as positive cells/mm2. CD4+ T cells were characterized by Foxp3 and CD4 double IHC, and results were expressed as CD4+cells/mm2, Foxp3+ cells /mm2 and CD4-Foxp3+cells /mm2. IL-10, Foxp3, CD4 and double staining counts were differentiated between germinal center (GC) and interfollicular (IF) regions of the tonsil.Four patients were primary infected (PI), 3 with reactivation (R), 8 healthy carriers (HC) and 3 no infected (NI). There was a significant difference in the CD4+, Foxp3+ and CD4/Foxp3+ cell count between the GC and the IF regions of the tonsil in the entire cohort (p˂0,0001). No differences were observed in CD4+, Foxp3+ and CD4-Foxp3+ cell number among PI, R and HC, as well as between infected and NI patients (p>0.05). When latency II (LMP1+) vs III (LMP1+, EBNA2+) profiles were compared, also no differences were observed. Statistical significant correlation were proved between Foxp3+ and CD4-Foxp3+cells with LMP1+ cells in infected patients (p=0.0055; r=0.7198 in both cases, Spearman). There was no correlation of EBNA2 with foxp3, CD4 and doubles(p>0.05).CD4+ cells displayed a statistical positive correlation with IL-10+ cells in the entire series, in particular in infected patients (p=0.0312, r=0.5084; p=0.0067, r=0.6663). So far, the recruitment of CD4+T cells prevails outside the GC. The expression of LMP1 latent protein may recruit CD4+ T cells that express Foxp3 to induce immuneregulation. Cooperation between CD4+ T cells and IL-10 could also be involved in this regulation