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Effector CD8 T Cells Possess Suppressor Function after 4-1BB and Toll-like Receptor Triggering
Lara Myers, Chikara Takahashi, Robert S. Mittler, Robert J. Rossi and Anthony T. Vella
Proceedings of the National Academy of Sciences of the United States of America
Vol. 100, No. 9 (Apr. 29, 2003), pp. 5348-5353
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3139715
Page Count: 6
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To better understand how innate and adaptive immune responses interact with each other, we combined 4-1BB T cell costimulation with specific adjuvants to determine whether these treatments would influence specific T cell expansion and function in vivo. In the presence of 4-1BB ligation and Toll-like receptor 3 (TLR)3 and/or TLR4 triggering, CD8 T cell clonal expansion and survival was augmented profoundly. Specific T cells primed in vivo with TLR ligands responded normally to in vitro recall stimulus, but, surprisingly, copriming with 4-1BB costimulation significantly impaired the recall response even though many more specific effector T cells were rescued in vivo. Here, we demonstrate that the rescued CD8 T cells suppressed CD4 T cell proliferation via a type β transforming growth factor-dependent mechanism. Thus, 4-1BB and TLR ligands induce survival of specific effector CD8 T cells with suppressive recall potential, which may explain the dual role that 4-1BB activation plays in mediating tumor clearance and prevention of autoimmune disease.
Proceedings of the National Academy of Sciences of the United States of America © 2003 National Academy of Sciences