Direct stimulation of T cells by type I IFN enhances the CD8+ T cell response during cross-priming.
Type I IFN (IFN-alphabeta), which is produced rapidly in response to infection, plays a key role in innate immunity and also acts as a stimulus for the adaptive immune response. We have investigated how IFN-alphabeta induces cross-priming, comparing CD8+ T cell responses generated against soluble protein Ags in the presence or absence of IFN-alphabeta. Injection of IFN-alpha was found to prolong the proliferation and expansion of Ag-specific CD8+ T cells, which was associated with marked up-regulation of IL-2 and IL-15 receptors on Ag-specific cells and expression of IL-15 in the draining lymph node. Surprisingly, neither IL-2 nor IL-15 was required for IFN-alpha-induced cross-priming. Conversely, expression of the IFN-alphabetaR by T cells was shown to be necessary for effective stimulation of the response by IFN-alpha. The finding that T cells represent direct targets of IFN-alphabeta-mediated stimulation reveals an additional mechanism by which the innate response to infection promotes adaptive immunity.
The Edward Jenner Institute for Vaccine Research, Compton, United Kingdom.
Agnes
A
Le Bon
Vanessa
V
Durand
Elisabeth
E
Kamphuis
Clare
C
Thompson
Silvia
S
Bulfone-Paus
Cornelia
C
Rossmann
Ulrich
U
Kalinke
David F
DF
Tough
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D049109:Cell Proliferation; D003429:Cross Reactions; D018076:DNA, Complementary / Q000235:genetics; D007113:Immunity, Innate; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D019409:Interleukin-15 / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011828:Radiation Chimera / Q000276:immunology; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism
D018076:DNA, Complementary; C508025:Il15ra protein, mouse; D016898:Interferon-alpha; D019409:Interleukin-15; D008565:Membrane Proteins; D017471:Receptors, Interferon; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D053633:Receptor, Interferon alpha-beta; D010047:Ovalbumin