Overcoming original antigenic sin to generate new CD8 T cell IFN-gamma responses in an antigen-experienced host.
The failure to mount effective immunity to virus variants in a previously virus-infected host is known as original antigenic sin. We have previously shown that prior immunity to a virus capsid protein inhibits induction by immunization of an IFN-gamma CD8+ T cell response to an epitope linked to the capsid protein. We now demonstrate that capsid protein-primed CD4+ T cells secrete IL-10 in response to capsid protein presented by dendritic cells, and deviate CD8+ T cells responding to a linked MHC class I-restricted epitope to reduce IFN-gamma production. Neutralizing IL-10 while delivering further linked epitope, either in vitro or in vivo, restores induction by immunization of an Ag-specific IFN-gamma response to the epitope. This finding demonstrates a strategy for overcoming inhibition of MHC class I epitopes upon immunization of a host already primed to Ag, which may facilitate immunotherapy for chronic viral infection or cancer.
Liu
Xiao Song
XS
Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Woolloongabba, Brisbane, Australia. xliu@cicr.uq.edu.au
Dyer
Joanne
J
Leggatt
Graham R
GR
Fernando
Germain J P
GJ
Zhong
Jie
J
Thomas
Ranjeny
R
Frazer
Ian H
IH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D018123:Receptors, Interleukin / Q000276:immunology; D053701:Receptors, Interleukin-10; D015375:Receptors, Interleukin-2 / Q000276:immunology; D018411:Spodoptera
C423449:CpG ODN 1826; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D015375:Receptors, Interleukin-2; C059731:oncogene protein E7, Human papillomavirus type 16; D016753:Interleukin-10; D007371:Interferon-gamma; D004247:DNA