期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 20, 页码 7835-7840出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1116058109
关键词
astrocyte; two-photon microscopy; Stat1; neuroimmunology; adenoviruses
资金
- National Institutes of Health/National Institute of Neurological Disorders and Stroke [1U01 NS052465.01, 1R01-NS 057711, 1R21-NSO54143, 1 R01 NS 054193, R01 NS 42893]
- Bram and Elaine Goldsmith
- Medallions Group Endowed Chairs in Gene Therapeutics
- Drown Foundation
- Linda Tallen and David Paul Kane Foundation
- Board of Governors at Cedars-Sinai Medical Center
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-gamma 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-gamma 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-gamma are more widespread.
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