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Biphasic role of 4-1BB in the regulation of mouse cytomegalovirus-specific CD8+ T cells

Humphreys, Ian R., Lee, Seung-Woo, Jones, Morgan, Loewendorf, Andrea, Gostick, Emma, Price, David A., Benedict, Chris A., Ware, Carl F. and Croft, Michael 2010. Biphasic role of 4-1BB in the regulation of mouse cytomegalovirus-specific CD8+ T cells. European Journal of Immunology 40 (10) , pp. 2762-2768. 10.1002/eji.200940256

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Abstract

The initial requirement for the emergence of CMV-specific CD8+ T cells is poorly understood. Mice deficient in the cosignaling TNF superfamily member, 4-1BB, surprisingly developed exaggerated early CD8+ T-cell responses to mouse CMV (MCMV). CD8+ T cells directed against acute MCMV epitopes were enhanced, demonstrating that 4-1BB naturally antagonizes these primary populations. Paradoxically, 4-1BB-deficient mice displayed reduced accumulation of memory CD8+ T cells that expand during chronic/latent infection. Importantly, the canonical TNF-related ligand, 4-1BBL, promoted the accumulation of these memory CD8+ T cells, whereas suppression of acute CD8+ T cells was independent of 4-1BBL. These data highlight the dual nature of the 4-1BB/4-1BBL system in mediating both stimulatory and inhibitory cosignaling activities during the generation of anti-MCMV immunity.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology > QR355 Virology
Uncontrolled Keywords: 4-1BB; CD8+ T cells; CMV; Memory
Publisher: Wiley-Blackwell
ISSN: 0014-2980
Funders: National Institutes of Health, Wellcome Trust, Medical Research Council
Last Modified: 06 Feb 2019 22:14
URI: http://orca.cf.ac.uk/id/eprint/22552

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