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This Article Full Text (PDF) All Versions of this Article: jimmunol.0802047v1 183/1/51    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Google Scholar Articles by Liu, X. S. Articles by Frazer, I. H. PubMed PubMed Citation Articles by Liu, X. S. Articles by Frazer, I. H.

IFN- Promotes Generation of IL-10 Secreting CD4⁺ T Cells that Suppress Generation of CD8 Responses in an Antigen-Experienced Host

Xiao Song Liu^*, Joanne Leerberg^*, Kelli MacDonald, Graham R. Leggatt^* and Ian H. Frazer^*

^*Immunology Program, University of Queensland Diamantina Institute for Cancer, Immunology and Metabolic Medicine, Princess Alexandra Hospital, Woolloongabba, Brisbane, Australia; and Bone Marrow Transplantation Laboratory, Queensland Institute of Medical Research, Herston, Queensland, Australia

Ags characterizing tumors or chronic viral infection are generally presented to the host immune system before specific immunotherapy is initiated, and consequent generation of regulatory CD4⁺ T cells can inhibit induction of desired effector CD8 T cell responses. IL-10 produced in response to ongoing Ag exposure inhibits generation of CD8 T cells in an Ag-experienced host. We now show that this IL-10 is produced by Ag experienced CD4⁺ glucocorticoid-induced tumor necrosis factor receptor⁺ T cells that also secrete IFN- upon antigenic stimulation, that IL-10 secretion by these cells is enhanced through IFN- signaling, and, unexpectedly, that IFN- signaling is required for inhibition of generation of Ag-specific CD8 T cell responses in an Ag-experienced host. Systemic inhibition of both IL-10 and IFN- at the time of immunization may therefore facilitate induction of effective immunotherapeutic responses against tumor specific and viral Ags.

Address correspondence and reprint requests to Prof. Ian Frazer, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia. E-mail address: i.frazer{at}uq.edu.au.

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