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IL-10 Mediates Suppression of the CD8 T Cell IFN- Response to a Novel Viral Epitope in a Primed Host¹

Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Woolloongabba, Brisbane, Australia

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- 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--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.

This article has been cited by other articles:

				X. S. Liu, J. Leerberg, K. MacDonald, G. R. Leggatt, and I. H. Frazer IFN-{gamma} Promotes Generation of IL-10 Secreting CD4+ T Cells that Suppress Generation of CD8 Responses in an Antigen-Experienced Host J. Immunol., July 1, 2009; 183(1): 51 - 58. [Abstract] [Full Text] [PDF]

				X. S. Liu, J. Dyer, G. R. Leggatt, G. J. P. Fernando, J. Zhong, R. Thomas, and I. H. Frazer Overcoming Original Antigenic Sin to Generate New CD8 T Cell IFN-{gamma} Responses in an Antigen-Experienced Host. J. Immunol., September 1, 2006; 177(5): 2873 - 2879. [Abstract] [Full Text] [PDF]