IL-10 suppresses CD8 responses to a novel viral epitope & 11/03 JI

In the 11/1/03 Journal of Immunology article titled "IL-10 Mediates
Suppression of the CD8 T Cell IFN-gamma Response to a Novel Viral
Epitope in a Primed Host," Liu et al. state:

"In this study, it is demonstrated that the CD8 T cell IFN-gamma
response to a novel epitope, induced when animals are immunized with the
epitope incorporated into PV VLPs [virus-like particles] as a carrier
Ag, is markedly reduced by pre-existing immunity to the VLP. A reduced
response requires IL-10 production, is local to the site of carrier
protein delivery, and is independent of Ab to the carrier protein. These
findings shed light on the immune mechanisms underlying the phenomenon
referred to as original antigenic sin, commonly attributed to preformed
Ab to the carrier protein, and also explain in part the difficulty
observed in inducing novel CD8-restricted IFN-gamma immune responses to
a tumor Ag, when an ineffective immune response to that tumor Ag is
already present."

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Liu XS, Xu Y, Hardy L, Khammanivong V, Zhao W, Fernando GJ, Leggatt GR,
Frazer IH. IL-10 Mediates Suppression of the CD8 T Cell IFN-gamma
Response to a Novel Viral Epitope in a Primed Host. J Immunol. 2003 Nov
1;171(9):4765-72.

Centre for Immunology and Cancer Research, Princess Alexandra Hospital,
University of Queensland, Woolloongabba, Brisbane, Australia.
E-mail: [EMAIL PROTECTED]

Abstract: 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.