Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells.

Nicholas Stephen Rennie Sanderson, Mariana Puntel, Kurt M Kroeger, Niyati S Bondale, Mark Swerdlow, Niloufar Iranmanesh, Hideo Yagita, Ahmed Ibrahim, Maria G Castro, Pedro R Lowenstein

Proceedings of the National Academy of Sciences of the United States of America 2012 May 15

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Following antigen recognition on target cells, effector T cells establish immunological synapses and secrete cytokines. It is thought that T cells secrete cytokines in one of two modes: either synaptically (i.e., toward antigenic target cells) or multidirectionally, affecting a wider population of cells. This paradigm predicts that synaptically secreted cytokines such as IFN-γ will preferentially signal to antigenic target cells contacted by the T cell through an immunological synapse. Despite its physiological significance, this prediction has never been tested. We developed a live-cell imaging system to compare the responses of target cells and nonantigenic bystanders to IFN-γ secreted by CD8+, antigen-specific, cytotoxic T cells. Both target cells and surrounding nontarget cells respond robustly. This pattern of response was detected even at minimal antigenic T-cell stimulation using low doses of antigenic peptide, or altered peptide ligands. Although cytotoxic immunological synapses restrict killing to antigenic target cells, the effects of IFN-γ are more widespread.

Citation

Nicholas Stephen Rennie Sanderson, Mariana Puntel, Kurt M Kroeger, Niyati S Bondale, Mark Swerdlow, Niloufar Iranmanesh, Hideo Yagita, Ahmed Ibrahim, Maria G Castro, Pedro R Lowenstein. Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells. Proceedings of the National Academy of Sciences of the United States of America. 2012 May 15;109(20):7835-40