Innate Inflammatory Signals Induced by Various Pathogens Differentially Dictate the IFN-I Dependence of CD8 T Cells for Clonal Expansion and Memory Formation

• Published in: Journal of Immunology 2006-08, Vol.177 (3), p.1746-1754
• Main Authors: Thompson, Lucas J, Kolumam, Ganesh A, Thomas, Sunil, Murali-Krishna, Kaja
• Format: Article
• Language: English
• Subjects: Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - microbiology; Antigen-Presenting Cells - virology; Antigens, Bacterial - biosynthesis; Antigens, Bacterial - metabolism; Antigens, Viral - biosynthesis; Antigens, Viral - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - microbiology; CD8-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - virology; Cell Differentiation - immunology; Cell Proliferation; Clone Cells; Immunity, Innate; Immunologic Memory; Inflammation - immunology; Inflammation - microbiology; Inflammation - virology; Interferon Type I - physiology; Listeria monocytogenes; Listeriosis - immunology; Listeriosis - microbiology; Listeriosis - pathology; Lymphocytic Choriomeningitis - immunology; Lymphocytic Choriomeningitis - pathology; Lymphocytic Choriomeningitis - virology; Lymphocytic choriomeningitis virus; Mice; Mice, Inbred C57BL; Mice, Knockout; Rhabdoviridae Infections - immunology; Rhabdoviridae Infections - pathology; Rhabdoviridae Infections - virology; Signal Transduction - immunology; Vaccinia - immunology; Vaccinia - pathology; Vaccinia - virology; Vaccinia virus; Vesicular stomatitis virus
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.177.3.1746

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.