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Memory CD8; +; T Cell Protection From Viral Reinfection Depends on Interleukin-33 Alarmin Signals

Baumann, Claudia and Fröhlich, Anja and Brunner, Tobias M. and Holecska, Vivien and Pinschewer, Daniel D. and Löhning, Max. (2019) Memory CD8; +; T Cell Protection From Viral Reinfection Depends on Interleukin-33 Alarmin Signals. Frontiers in immunology, 10. p. 1833.

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Official URL: https://edoc.unibas.ch/76546/

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Abstract

Memory CD8; +; cytotoxic T lymphocytes (CTLs) can protect against viral reinfection. However, the signals driving rapid memory CTL reactivation have remained ill-defined. Viral infections can trigger the release of the alarmin interleukin-33 (IL-33) from non-hematopoietic cells. IL-33 signals through its unique receptor ST2 to promote primary effector expansion and activation of CTLs. Here, we show that the transcription factor STAT4 regulated the expression of ST2 on CTLs; in vitro; and; in vivo; in primary infections with lymphocytic choriomeningitis virus (LCMV). In the primary antiviral response, IL-33 enhanced effector differentiation and antiviral cytokine production in a CTL-intrinsic manner. Further, using sequential adoptive transfers of LCMV-specific CD8; +; T cells, we deciphered the IL-33 dependence of circulating memory CTLs at various stages of their development. IL-33 was found dispensable for the formation and maintenance of memory CTLs, and its absence during priming did not affect their recall response. However, in line with the CTL-boosting role of IL-33 in primary LCMV infections, circulating memory CTLs required IL-33 for efficient secondary expansion, enhanced effector functions, and virus control upon challenge infection. Thus, beyond their effector-promoting activity in primary immune reactions, innate alarmin signals also drive memory T cell recall responses, which has implications for immunity to recurrent diseases.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Experimental Virology (Pinschewer)
UniBasel Contributors:Pinschewer, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1664-3224
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 May 2020 09:32
Deposited On:27 May 2020 09:32

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