Biphasic role of 4-1BB in the regulation of mouse cytomegalovirus-specific CD8 T cells
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- Title
- Biphasic role of 4-1BB in the regulation of mouse cytomegalovirus-specific CD8 T cells
- Authors
- Humphreys, IR; Lee, SW; Jones, M; Loewendorf, A; Gostick, E; Price, DA; Benedict, CA; Ware, CF; Croft, M
- Date Issued
- 2010-10
- Publisher
- European Journal of Immunology
- 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.
- Keywords
- 4-1BB; CD8(+) T cells; CMV; Memory; ALLOGENEIC BONE-MARROW; MURINE CYTOMEGALOVIRUS; MEMORY INFLATION; VIRAL-INFECTION; IN-VIVO; RESPONSES; COSTIMULATION; LIGAND; IMMUNITY; OX40
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/14200
- DOI
- 10.1002/EJI.200940256
- ISSN
- 0014-2980
- Article Type
- Article
- Citation
- EUROPEAN JOURNAL OF IMMUNOLOGY, vol. 40, no. 10, page. 2762 - 2768, 2010-10
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