T cells use two directionally distinct pathways for cytokine secretion.
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-gamma, were secreted into the synapse, whereas others, including tumor necrosis factor and the chemokine CCL3 (MIP-1alpha), 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.
Huse
Morgan
M
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA.
Lillemeier
Björn F
BF
Kuhns
Michael S
MS
Chen
Daniel S
DS
Davis
Mark M
MM
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines