Journal
IMMUNOLOGY
Volume 132, Issue 4, Pages 549-558Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2567.2010.03400.x
Keywords
CD8; cytotoxic T cells; CD4; helper T cells (Th cells; Th0; Th1; Th2; Th3; Th17); dendritic cells; inflammation; natural killer cells (NK cells)
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Funding
- National Institutes of Health [AI 48721]
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P>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-alpha (TNF-alpha) or type I interferon-alpha (IFN-alpha) also failed to prime CD8(+) T-cell responses in the absence of help. Injection of TNF-alpha increased lymph node cellularity, but did not generate help-independent CD8(+) T-cell responses. In contrast, CD4-depleted mice injected with IFN-alpha 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-alpha 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-alpha secretion is stimulated by tissue damage, infection, or autoimmune disease.
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