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

Abstract

Following antigen recognition on target cells, effector T cellsestablish immunological synapses and secrete cytokines. It isthought that T cells secrete cytokines in one of two modes: eithersynaptically (i.e., toward antigenic target cells) or multidirectionally,affecting a wider population of cells. This paradigm predicts thatsynaptically secreted cytokines such as IFN-γ will preferentially signalto antigenic target cells contacted by the T cell through an immunologicalsynapse. Despite its physiological significance, this predictionhas never been tested. We developed a live-cell imaging system tocompare the responses of target cells and nonantigenic bystandersto IFN-γ secreted by CD8+, antigen-specific, cytotoxic T cells. Bothtarget cells and surrounding nontarget cells respond robustly. Thispattern of response was detected even at minimal antigenic T-cellstimulation using low doses of antigenic peptide, or altered peptideligands. Although cytotoxic immunological synapses restrict killingto antigenic target cells, the effects of IFN-γ are more widespread.