Innate inflammatory signals induced by various pathogens differentially dictate the IFN-I dependence of CD8 T cells for clonal expansion and memory formation.
Type-I IFNs (IFN-I) provide direct survival signals to T cells during Ag-driven proliferation. Because IFN-I production differs depending on the pathogen, we assessed CD8 T cell requirement for direct IFN-I signals during responses to vaccinia virus (VV), vesicular stomatitis virus (VSV), lymphocytic choriomeningitis virus (LCMV), and Listeria monocytogenes (LM) immunizations in vivo. IFN-I-receptor-deficient (IFN-IR(o)) CD8 T cells expanded 3- to 5-fold less and formed a diminished memory pool compared with wild-type (WT) CD8 T cells in response to VV, VSV, or LM. WT CD8 T cells expanded more robustly in response to LCMV-encoded Ags than to Ags encoded by the other three pathogens, and under these conditions the lack of direct IFN-I signals inhibited their expansion by approximately 100-fold. To test whether the high antigenic-load provided by LCMV caused greater expansion and greater IFN-I dependency, we primed WT and IFN-IR(o) OVA-specific OT-1 CD8 T cells with a fixed-number of OVA-peptide-pulsed dendritic cells along with adjuvant effect provided by LCMV, VV, VSV, or LM. Both WT and IFN-IR(o) OT-1 cells were recruited, proliferated, and differentiated into effectors in all the four cases. However, WT OT-1 cells expanded similarly in all four cases. IFN-IR(o) OT-1 cells expanded approximately 20-fold less than the WT OT-1 CD8 T cells when LCMV was used as adjuvant, whereas their expansion was affected only marginally when VV, VSV, or LM were used as adjuvants. Thus, innate/inflammatory signals induced by different pathogens contribute to CD8 T cell expansion and memory formation via distinct levels of IFN-I dependence.
Thompson
Lucas J
LJ
Department of Immunology and Washington National Primate Center, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA.
Kolumam
Ganesh A
GA
Thomas
Sunil
S
Murali-Krishna
Kaja
K
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000382:microbiology / Q000821:virology; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000378:metabolism; D000956:Antigens, Viral / Q000096:biosynthesis / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology* / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002999:Clone Cells; D007113:Immunity, Innate; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000821:virology; D007370:Interferon Type I / Q000502:physiology*; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology; D015398:Signal Transduction / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology / Q000473:pathology* / Q000821:virology
D000942:Antigens, Bacterial; D000956:Antigens, Viral; D007370:Interferon Type I