Analysis of PD1/PDL1 pathway in primary and persistent Epstein Barr virus infection

AMARILLO ME; MOYANO, A.; FERRESSINI GERPE, N.M.; DE MATTEO, E; PRECIADO, M. V.; PAOLA ANDREA CHABAY

Mar del Plata

Congreso; Reunión anual de Sociedades de Biociencias; 2023

Our aim was to study CD4+ and PD1+ cells and their relationship with the contribution of PDL1 from macrophages in the tonsils of children infected with Epstein Barr infection. Thirty-eight patients undergoing tolsillectomy were studied. EBV infection status was defined by serology. Immunohistochemistry (IHC) was performed for IL-10, TGF-β, CD4, PD1, LMP1 and EBNA2 proteins. Double staining was performed to characterize both CD68/PDL1+ and CD163/PDL1+ macrophages.IL-10, TGF-β, CD4, PD1 and double staining counts were differentiated between germinal center (GC) and interfollicular (IF) regions of the tonsil. Results were expressed as positive cells/mm2.Twelve patients were primary infected (PI), 8 with reactivation (R), 14 healthy carriers (HC) and 4 no infected (NI). Five patients presented a latency profile 0, 10 a latency profile I, 9 a latency profile II and 10 a latency profile III.As expected, the PD1+ cell count was higher in the GC than in the IF region (p˂0.0001). There were no significant differences when comparing this count between the different stages of infection (P>0.05). There was a positive correlation between CD4+ and PD1+ count in the group of patients with a latency II profile only (p=0.0345; r=0.7033). There was a negative correlation between PD1 and TGF-β particularly in GC (r=-0.3526; p=0.0478) and no correlation of PD1 with IL10 was observed. There was a negative correlation between PD1 and CD163/PDL1 mostly in the tonsil GC (r=-0.5539; P=0.0061). In contrast, no correlation was observed between PD1 and CD68/PDL1 (P>0.05). When CD4 count was compared with CD68/PDL1 and CD163/PDL1 there was no correlation (P>0.05).Conclusion: EBV infection does not seems to induce an exhausted PD1/PDL1 environment. Furthermore, at the GC, PD1 might be inversely influenced by exhaustion ligands and anti-inflammatory cytokines. Only the expression of the main viral oncoprotein, LMP1, have influence on PD1+ cells expressed by CD4+ T cells.