Role of GrzB+ CD4+ lymphocytes associated with EBV infection in tonsils of pediatric patients in Argentina

AMARILLO ME; MOYANO A; FERRESSINI GERPE, N. M.; DE MATTEO E; PRECIADO MV; CHABAY, P.

Misoula

Congreso; International Herpesvirus Workshop; 2023

International Herpesvirus Workshop

Epstein Barr Virus (EBV) infeciton is efficiently controlled by the immune system. However, a failure may develop EBV-associated lymphoma from the germinal center (GC). Our aim was to study CD4+ T cell response, specifically Granzyme B+ (GrzB+) CD4+ cytotoxic cells in pediatric EBV infection to clarify viral contribution to lymphomagenesis. We studied 50 patients undergoing tonsillectomy. EBV infection status was defined by serology. Immunohistochemistry (IHC) for viral proteins LMP1 and EBNA2 and in situ hybridization (ISH) for EBERS were performed in order to stratify patients into Latency 0, I, II and III. The IHC results were expressed as positive cells/cm2. GrzB+ CD4+ T cells were characterized by GrzB and CD4 double IHC, expressed as GrzB+ CD4+ cells/mm2. GrzB+ CD4+, and differentiated between germinal center (GC) and interfollicular (IF) regions.16 patients were primary infected (PI), 9 with reactivation (R), 21 healthy carrers (HC) and 4 non infected (NI). There was a significantly higher CD4+ GrzB+ T cell count at the IF region in the entire cohort (P˂0.0001). This difference is conserved when we study each of the infection status separately (p˂0.05). In addition, significantly higher CD4+GrzB+ cell count was observed in PI patients were compared to HC (p=0.0370). Patients with latency profile III had a lower GrzB+CD4+ count compared to patients with latency profile II (P=0.0128) and latency I (P=0.0317).The increased CD4+GrzB+ cells count in PI patients, in which latency I and II prevailed, may indicate a key role for these cells in active viral infection. Furthermore, the lower recruitment of CD4+ GrzB+ T lymphocytes in patients with latency III suggests that they may be specifically involved in the modulation of latency.