Dynamic control of self-specific CD8+ T cell responses via a combination of signals mediated by dendritic cells.
It is acknowledged that T cell interactions with mature dendritic cells (DC) lead to immunity, whereas interactions with immature DC lead to tolerance induction. Using a transgenic murine system, we have examined how DC expressing self-peptides control naive, self-reactive CD8+ T cell responses in vitro and in vivo. We have shown, for the first time, that immature DC can also stimulate productive activation of naive self-specific CD8+ T cells, which results in extensive proliferation, the expression of a highly activated cell surface phenotype, and differentiation into autoimmune CTL. Conversely, mature DC can induce abortive activation of naive CD8+ T cells, which is characterized by low-level proliferation, the expression of a partially activated cell surface phenotype which does not result in autoimmune CTL. Critically, both CD8+ T cell responses are determined by a combination of signals mediated by the DC, and that altering any one of these signals dramatically shifts the balance between autoimmunity and self-tolerance induction. We hypothesize that DC maintain the steady state of self-tolerance among self-specific CD8+ T cells in an active and dynamic manner, licensing productive immune responses against self-tissues only when required.
Raveney
Ben J E
BJ
Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, University Walk, Bristol, United Kingdom.
Morgan
David J
DJ
D000818:Animals; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D017634:Self Tolerance; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D011948:Receptors, Antigen, T-Cell