@article {Ontiveros:2011:0019-2805:549,
title = "Type I interferon supports primary CD8+ T-cell responses to peptide-pulsed dendritic cells in the absence of CD4+ T-cell help",
journal = "Immunology",
parent_itemid = "infobike://bsc/imm",
publishercode ="bp",
year = "2011",
volume = "132",
number = "4",
publication date ="2011-04-01T00:00:00",
pages = "549-558",
itemtype = "ARTICLE",
issn = "0019-2805",
eissn = "1365-2567",
url = "https://www.ingentaconnect.com/content/bsc/imm/2011/00000132/00000004/art00010",
doi = "doi:10.1111/j.1365-2567.2010.03400.x",
keyword = "CD8/cytotoxic T cells, inflammation, CD4/helper T cells (Th cells, Th0, Th1, Th2, Th3, Th17), natural killer cells (NK cells), dendritic cells",
author = "Ontiveros, Fernando and Wilson, Elizabeth B. and Livingstone, Alexandra M.",
abstract = "Summary CD8+ T-cell responses to non-pathogen, cell-associated antigens such as minor alloantigens or peptide-pulsed dendritic cells (DC) are usually strongly dependent on help from CD4+ T cells. However, some studies have described help-independent primary CD8+ T-cell responses to cell-associated antigens, using immunization strategies likely to trigger natural killer (NK) cell activation and inflammatory cytokine production. We asked whether NK cell activation by MHC I-deficient cells, or administration of inflammatory cytokines, could support CD4+ T-cell help-independent primary responses to peptide-pulsed DC. Injection of MHC I-deficient cells cross-primed CD8+ T-cell responses to the protein antigen ovalbumin (OVA) and the male antigen HY, but did not stimulate CD8+ T-cell responses in CD4-depleted mice; hence NK cell stimulation by MHC I-deficient cells did not replace CD4+ T-cell help in our experiments. Dendritic cells cultured with tumour necrosis factor- (TNF-) or type I interferon- (IFN-) also failed to prime CD8+ T-cell responses in the absence of help. Injection of TNF- increased lymph node cellularity, but did not generate help-independent CD8+ T-cell responses. In contrast, CD4-depleted mice injected with IFN- made substantial primary CD8+ T-cell responses to peptide-pulsed DC. Mice deficient for the type I IFN receptor (IFNR1) made CD8+ T-cell responses to IFNR1-deficient, peptide-pulsed DC; hence IFN- does not appear to be a downstream mediator of CD4+ T-cell help. We suggest that primary CD8+ T-cell responses will become help-independent whenever endogenous IFN- secretion is stimulated by tissue damage, infection, or autoimmune disease.",
}