T Cell Help Amplifies Innate Signals in CD8(+) DCs for Optimal CD8(+) T Cell Priming

Marie Greyer; Paul G Whitney; Angus T Stock; Gayle M Davey; Christina Tebartz; Annabell Bachem; Justine D Mintern; Richard A Strugnell; Stephen J Turner; Thomas Gebhardt; Meredith O'Keeffe; William R Heath; Sammy Bedoui

doi:10.1016/j.celrep.2015.12.058

T Cell Help Amplifies Innate Signals in CD8(+) DCs for Optimal CD8(+) T Cell Priming

Cell Rep. 2016 Jan 26;14(3):586-597. doi: 10.1016/j.celrep.2015.12.058. Epub 2016 Jan 7.

Affiliations

¹ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
² Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia.
³ Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3088, Australia.
⁴ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: [email protected].

PMID: 26774484
DOI: 10.1016/j.celrep.2015.12.058

Abstract

DCs often require stimulation from CD4(+) T cells to propagate CD8(+) T cell responses, but precisely how T cell help optimizes the priming capacity of DCs and why this appears to differ between varying types of CD8(+) T cell immunity remains unclear. We show that CD8(+) T cell priming upon HSV-1 skin infection depended on DCs receiving stimulation from both IFN-α/β and CD4(+) T cells to provide IL-15. This was not an additive effect but resulted from CD4(+) T cells amplifying DC production of IL-15 in response to IFN-α/β. We also observed that increased innate stimulation reversed the helper dependence of CD8(+) T cell priming and that the innate stimulus, rather than the CD4(+) T cells themselves, determined how "help'" was integrated into the priming response by DCs. These findings identify T cell help as a flexible means to amplify varying suboptimal innate signals in DCs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism
CD40 Antigens / metabolism
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / metabolism*
Chemokines / metabolism
Dendritic Cells / drug effects
Dendritic Cells / immunology
Dendritic Cells / metabolism*
Herpesvirus 1, Human / physiology
Humans
Interferon-alpha / genetics
Interferon-alpha / metabolism
Interferon-alpha / pharmacology
Interferon-beta / metabolism
Interleukin-15 / metabolism
Interleukin-6 / metabolism
Lymph Nodes / cytology
Lymph Nodes / immunology
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Receptor, Interferon alpha-beta / deficiency
Receptor, Interferon alpha-beta / genetics
Recombinant Proteins / biosynthesis
Recombinant Proteins / isolation & purification
Recombinant Proteins / pharmacology
Skin Diseases / pathology
Skin Diseases / virology
T-Lymphocytes, Helper-Inducer / immunology
T-Lymphocytes, Helper-Inducer / metabolism*

Substances

CD40 Antigens
Chemokines
Ifnar2 protein, mouse
Interferon-alpha
Interleukin-15
Interleukin-6
Recombinant Proteins
Receptor, Interferon alpha-beta
Interferon-beta