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A Role for the Transcriptional Repressor Blimp-1 in CD8+ T Cell Exhaustion during Chronic Viral Infection
Open accessAbstract
Summary T cell exhaustion is common during chronic infections and can prevent optimal immunity. While recent studies have demonstrated the importance of inhibitory receptors and other pathways in T cell exhaustion, the underlying transcriptional mechanisms are unknown. Here, we define a role for the transcription factor Blimp-1 in CD8 T cell exhaustion during chronic viral infection. Blimp-1 repressed key aspects of normal memory CD8 T cell differentiation and promoted high expression of inhibitory receptors during chronic infection. These cardinal features of CD8 T cell exhaustion were corrected by conditionally deleting Blimp-1. While high expression of Blimp-1 fostered aspects of CD8 T cell exhaustion, haploinsufficiency indicated that moderate Blimp-1 expression sustained some effector function during chronic viral infection. Thus, we identify Blimp-1 as a transcriptional regulator of CD8 T cell exhaustion during chronic viral infection and propose that Blimp-1 acts as a transcriptional rheostat balancing effector function and T cell exhaustion.
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Cites
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103
Self-citationJoshi, N. S., Cui, W., Chandele, A., Lee, H. K., Urso, D. R., Hagman, J., Gapin, L., & Kaech, S. M. (2007) · Immunity · doi:10.1016/j.immuni.2007.07.010 · Cited by 1,861
HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function
Appay, V., Nixon, D. F., Donahoe, S. M., Gillespie, G. M. A., Dong, T., King, A., Ogg, G. S., Spiegel, H. M. L., Conlon, C., Spina, C. A., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.1.63 · Cited by 871
Cited by
Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652
Self-citationWherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062
Self-citationFollicular Helper CD4 T Cells (T FH )
Crotty, S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101400 · Cited by 2,738
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Sakuishi, K., Apetoh, L., Sullivan, J. M., Blazar, B. R., Kuchroo, V. K., & Anderson, A. C. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100643 · Cited by 2,072
Long, A. H., Haso, W. M., Shern, J. F., Wanhainen, K. M., Murgai, M., Ingaramo, M., Smith, J. P., Walker, A. J., Kohler, M. E., Venkateshwara, V. R., et al. (2015) · Nature Medicine · doi:10.1038/nm.3838 · Cited by 1,815
Metadata
- Authors
- Shin, H., Blackburn, S. D., Intlekofer, A. M., Kao, C., Angelosanto, J. M., Reiner, S. L., & Wherry, E. J.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 31
- Issue
- 2
- Pages
- 309-320
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1987337968
- Cited by
- 481
- References
- 3
- FWCI
- 12.22
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Shin, H., Blackburn, S. D., Intlekofer, A. M., Kao, C., Angelosanto, J. M., Reiner, S. L., & Wherry, E. J. (2009). A Role for the Transcriptional Repressor Blimp-1 in CD8+ T Cell Exhaustion during Chronic Viral Infection. Immunity. https://doi.org/10.1016/j.immuni.2009.06.019
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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