| Popis: |
Healthy EBV seropositive donors tested for the ability to mount Th responses against LMP1 responded with secretion of high levels of the immunosuppressive cytokine IL-10 which was secreted from cells phenotypically analogous to the Tr1 class of regulatory T-cells. The epitopes inducing this IL-10 secretion were clustered in the hydrophobic, transmembrane half of the protein that corresponded to a cluster of high affinity MHC class II binding domains. Since the LMP1 induced TO cells could effectively suppress immune responses in an IL- 10 dependent manner, it seems likely that the induction of regulatory T-cells serves to prevent anti-EBV immune responses and aid viral persistence. PBMC and HLIL from HL patients also responded to stimulation with LMP1 by predominantly secreting IL-10. However, these patients appeared to mount weaker responses compared to healthy donors. In addition, a defect in their ability to mount Th1 responses against a range of control stimuli was documented. HL patient HLIL were highly enriched for populations of both Tr1and CD4CD25 regulatory T-cells, which were strongly suppressive. Such enriched populations of regulatory T-cells may be induced by LMP1 in EBV positive cases of HL and will act to prevent anti-tumour immune responses and aid tumour growth and persistence. Thus the Th cell response to LMP1 is dominated by the induction of regulatory T-cells in both latently infected donors and HL patients. This strategy of induction of Tr cells should serve to protect EBV infected cells (either latently infected B-cells or H-RS cells) from clearance by the host. This strategy of immune evasion via the induction of Tr cells may well be found with other persistent viral infections and tumours. |
