Nature Immunology 7, 247 - 255 (2006)
Published online: 29 January 2006; | doi:10.1038/ni1304
T cells use two directionally distinct pathways for cytokine secretionMorgan Huse1, Björn F Lillemeier1, Michael S Kuhns1, Daniel S Chen1, 2
& Mark M Davis1, 21
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA. 2
The Howard Hughes Medical Institute, Stanford, California 94305, USA.
Correspondence should be addressed to Mark M Davis mdavis@pmgm2.stanford.edu Activated T helper cells produce many cytokines, some of which are secreted through the immunological synapse toward the antigen-presenting cell. Here we have used immunocytochemistry, live-cell imaging and a surface-mediated secretion assay to show that there are two cytokine export pathways in T helper cells. Some cytokines, including interleukin 2 and interferon- , were secreted into the synapse, whereas others, including tumor necrosis factor and the chemokine CCL3 (MIP-1 ), were released multidirectionally. Each secretion pathway was associated with different trafficking proteins, indicating that they are molecularly distinct processes. These data suggest that T helper cells release some cytokines into the immunological synapse to impart specific communication and others multidirectionally to promote inflammation and to establish chemokine gradients.
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