CD8(+) lymphocytosis is recognized as the primary immunopathological response generated in primary EBV infection that may manifest itself as a benign lymphoproliferative disorder, infectious mononucleosis (IM). While CD4(+)FOXP3(+) T-regulatory cells (Treg cells) are well accepted to inhibit T-cell responses, it is puzzling why massive expansion of CD8(+) lymphocytes still occurs despite CD4(+)FOXP3(+) Treg cells are localized in tonsils, which are the port of entry of the virus. Understanding the interplay between the virologic and immunologic events that take place in tonsils in primary EBV infection is necessary to comprehend why IM preferentially develops in adolescents and the dynamics of CD4(+) Treg cell change that may occur in virus/pathogen infection in a broader setting.
