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


ABSTRACT: 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-? 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-? 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-? are more widespread.

SUBMITTER: Sanderson NS 

PROVIDER: S-EPMC3356634 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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

Sanderson Nicholas Stephen Rennie NS   Puntel Mariana M   Kroeger Kurt M KM   Bondale Niyati S NS   Swerdlow Mark M   Iranmanesh Niloufar N   Yagita Hideo H   Ibrahim Ahmed A   Castro Maria G MG   Lowenstein Pedro R PR  

Proceedings of the National Academy of Sciences of the United States of America 20120430 20


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 i  ...[more]

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