Journal article
Constitutive activation of Wnt signaling favors generation of memory CD8 T cells
The Journal of immunology (1950), Vol.184(3), pp.1191-1199
02/01/2010
DOI: 10.4049/jimmunol.0901199
PMCID: PMC2809813
PMID: 20026746
Abstract
T cell factor-1 (TCF-1) and lymphoid enhancer-binding factor 1, the effector transcription factors of the canonical Wnt pathway, are known to be critical for normal thymocyte development. However, it is largely unknown if it has a role in regulating mature T cell activation and T cell-mediated immune responses. In this study, we demonstrate that, like IL-7Ralpha and CD62L, TCF-1 and lymphoid enhancer-binding factor 1 exhibit dynamic expression changes during T cell responses, being highly expressed in naive T cells, downregulated in effector T cells, and upregulated again in memory T cells. Enforced expression of a p45 TCF-1 isoform limited the expansion of Ag-specific CD8 T cells in response to Listeria monocytogenes infection. However, when the p45 transgene was coupled with ectopic expression of stabilized beta-catenin, more Ag-specific memory CD8 T cells were generated, with enhanced ability to produce IL-2. Moreover, these memory CD8 T cells expanded to a larger number of secondary effectors and cleared bacteria faster when the immunized mice were rechallenged with virulent L. monocytogenes. Furthermore, in response to vaccinia virus or lymphocytic choriomeningitis virus infection, more Ag-specific memory CD8 T cells were generated in the presence of p45 and stabilized beta-catenin transgenes. Although activated Wnt signaling also resulted in larger numbers of Ag-specific memory CD4 T cells, their functional attributes and expansion after the secondary infection were not improved. Thus, constitutive activation of the canonical Wnt pathway favors memory CD8 T cell formation during initial immunization, resulting in enhanced immunity upon second encounter with the same pathogen.
Details
- Title: Subtitle
- Constitutive activation of Wnt signaling favors generation of memory CD8 T cells
- Creators
- Dong-Mei Zhao - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAShuyang YuXinyuan ZhouJodie S HaringWerner HeldVladimir P BadovinacJohn T HartyHai-Hui Xue
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.184(3), pp.1191-1199
- DOI
- 10.4049/jimmunol.0901199
- PMID
- 20026746
- PMCID
- PMC2809813
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- United States
- Grant note
- R01 AI050073 / NIAID NIH HHS R01 AI083286-01 / NIAID NIH HHS R01 AI042767-09 / NIAID NIH HHS R01 AI059752-05 / NIAID NIH HHS R01 AI046653-09 / NIAID NIH HHS R01 AI083286 / NIAID NIH HHS R01 HL095540-01 / NHLBI NIH HHS AI083286 / NIAID NIH HHS R01 AI042767 / NIAID NIH HHS R21 AI077504-01 / NIAID NIH HHS R21 AI042767 / NIAID NIH HHS AI042767 / NIAID NIH HHS R37 AI042767 / NIAID NIH HHS R21 AI077504-02 / NIAID NIH HHS AI059752 / NIAID NIH HHS AI046653 / NIAID NIH HHS R21 AI077504 / NIAID NIH HHS R01 AI050073-08 / NIAID NIH HHS AI077504 / NIAID NIH HHS R01 AI046653 / NIAID NIH HHS AI050073 / NIAID NIH HHS R01 AI059752 / NIAID NIH HHS HL095540 / NHLBI NIH HHS R01 HL095540 / NHLBI NIH HHS
- Language
- English
- Date published
- 02/01/2010
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984046830502771
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