IL-10 mediates suppression of the CD8 T cell IFN-gamma response to a novel viral epitope in a primed host.
Priming to Ag can inhibit subsequent induction of an immune response to a new epitope incorporated into that Ag, a phenomenon referred to as original antigenic sin. In this study, we show that prior immunity to a virus capsid can inhibit subsequent induction of the IFN-gamma effector T cell response to a novel CD8-restricted antigenic epitope associated with the virus capsid. Inhibition does not involve Ab to the virus capsid, as it is observed in animals lacking B cells. CD8-restricted virus-specific T cell responses are not required, as priming to virus without CTL induction is associated with inhibition. However, IL-10(-/-) mice, in contrast to IL-10(+/+) mice, generate CD8 T cell and Ab responses to novel epitopes incorporated into a virus capsid, even when priming to the capsid has resulted in high titer Ab to the capsid. Furthermore, capsid-primed mice, unable to mount a response to a novel epitope in the capsid protein, are nevertheless able to respond to the same novel epitope delivered independently of the capsid. Thus, inhibition of responsiveness to a novel epitope in a virus-primed animal is a consequence of secretion of IL-10 in response to presented Ag, which inhibits local generation of new CD8 IFN-gamma-secreting effector T cells. Induction of virus- or tumor Ag-specific CD8 effector T cells in the partially Ag-primed host may thus be facilitated by local neutralization of IL-10.
Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Woolloongabba, Brisbane, Australia.
Xiao Song
XS
Liu
Yan
Y
Xu
Lani
L
Hardy
Vithagna
V
Khammanivong
Weiming
W
Zhao
Germain J P
GJ
Fernando
Graham R
GR
Leggatt
Ian H
IH
Frazer
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000502:physiology; D052688:Bovine papillomavirus 1 / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D036022:Capsid Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D002417:Cattle; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D013491:Suppressor Factors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014771:Virion / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D036022:Capsid Proteins; C085208:E7 protein, Human papillomavirus 6b; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; D006241:Haptens; C085217:L1 protein, Bovine papillomavirus; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D013491:Suppressor Factors, Immunologic; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C075621:oncogene protein E7, Bovine papillomavirus type 1; C059731:oncogene protein E7, Human papillomavirus type 16; D016753:Interleukin-10; D007371:Interferon-gamma