CD4(+) T-cell help amplifies innate signals for primary CD8(+) T-cell immunity.
CD8(+) T cells provide an important component of protection against intracellular infections and cancer. Immune responses by these T cells involve a primary phase of effector expansion and differentiation, followed by a contraction phase leading to memory formation and, if antigen is re-encountered, a secondary expansion phase with more rapid differentiation. Both primary and secondary phases of CD8(+) T-cell immunity have been shown to depend on CD4(+) T-cell help, although during certain infections the primary phase is variable in this requirement. One explanation for such variability relates to the strength of associated inflammatory signals, with weak signals requiring help. Here, we focus on our studies that have dissected the requirements for help in the primary phase of the CTL response to herpes simplex virus, elucidating intricate interactions and communications between CD4(+) T cells, various dendritic cell subsets, and CD8(+) T cells. We place our studies in the context of others and describe a simple model of help where CD40 signaling amplifies innate signals to enable efficient CD8(+) T-cell expansion and differentiation. This model facilitates CTL induction to various different agents, without altering the qualitative innate signals that direct other important arms of immunity.
Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Parkville, Vic., Australia.
Sammy
S
Bedoui
Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Parkville, Vic., Australia.|The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Parkville, Vic., Australia.
William R
WR
Heath
Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Parkville, Vic., Australia.|The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Parkville, Vic., Australia.
Scott N
SN
Mueller
D056704:Adaptive Immunity; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007239:Infections / Q000276:immunology*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology*; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015704:CD4 Antigens; D019013:CD40 Antigens
cell activation; costimulation, CD40; cytotoxic T cells; dendritic cells; helper T cells