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CUTTING EDGE |
Department of Laboratory Medicine & Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455
In this study, we show that IFN-
can have a direct role in linking innate and adaptive responses by providing the "third signal" needed by naive CD8 T cells responding to Ag and costimulatory ligands. Stimulation of CD8 T cells in the absence of a third signal leads to proliferation, but clonal expansion is limited by poor survival and effector functions do not develop. We show that IFN- can provide the third signal directly to CD8 T cells via a STAT4-dependent pathway to stimulate survival, development of cytolytic function, and production of IFN-
. Provision of the third signal by either IFN- or IL-12 results in regulation of the expression of a number of genes, including several that encode proteins critical for effector function.
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A. Le Bon, C. Thompson, E. Kamphuis, V. Durand, C. Rossmann, U. Kalinke, and D. F. Tough Cutting Edge: Enhancement of Antibody Responses Through Direct Stimulation of B and T Cells by Type I IFN J. Immunol., February 15, 2006; 176(4): 2074 - 2078. [Abstract] [Full Text] [PDF]
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T. B. Thornley, M. A. Brehm, T. G. Markees, L. D. Shultz, J. P. Mordes, R. M. Welsh, A. A. Rossini, and D. L. Greiner TLR Agonists Abrogate Costimulation Blockade-Induced Prolongation of Skin Allografts J. Immunol., February 1, 2006; 176(3): 1561 - 1570. [Abstract] [Full Text] [PDF]
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M. P. Gil, R. Salomon, J. Louten, and C. A. Biron Modulation of STAT1 protein levels: a mechanism shaping CD8 T-cell responses in vivo Blood, February 1, 2006; 107(3): 987 - 993. [Abstract] [Full Text] [PDF]
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J. M. Curtsinger, D. C. Lins, C. M. Johnson, and M. F. Mescher Signal 3 Tolerant CD8 T Cells Degranulate in Response to Antigen but Lack Granzyme B to Mediate Cytolysis J. Immunol., October 1, 2005; 175(7): 4392 - 4399. [Abstract] [Full Text] [PDF]
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G. A. Kolumam, S. Thomas, L. J. Thompson, J. Sprent, and K. Murali-Krishna Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection J. Exp. Med., September 6, 2005; 202(5): 637 - 650. [Abstract] [Full Text] [PDF]
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