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A Th17-like developmental process leads to CD8+Tc17 cells with reduced cytotoxic activity

Authors :
Thomas Hünig
Anne Brüstle
Henrike Grothe
Thomas Kamradt
Karin Elflein
Hans-Willi Mittrücker
Michael Lohoff
Anna Guralnik
Magdalena Huber
Katharina Reinhard
Sylvia Heink
Source :
European Journal of Immunology. 39:1716-1725
Publication Year :
2009
Publisher :
Wiley, 2009.

Abstract

Activation of naive CD8(+) T cells with antigen in the absence of skewing cytokines triggers their differentiation into effector CTL, which induces death of target cells. We show that CD8(+) T cells activated in the presence of the cytokines IL-6 or IL-21 plus TGF-beta similar to CD4(+) T cells, develop into IL-17-producing (Tc17) cells. These cells display greatly suppressed cytotoxic function along with low levels of the CTL markers: T-box transcription factor Eomesodermin, granzyme B and IFN-gamma. Instead, these cells express hallmark molecules of Th17 program including retinoic acid receptor-related orphan receptor (ROR)gammat, RORalpha, IL-21 and IL-23R. The expression of the type 17 master regulator RORgammat is causally linked to Tc17 generation, because its overexpression stimulates production of IL-17 in the presence of IL-6 or IL-21. Both, upregulation of the type 17 program as well as suppression of CTL differentiation are STAT3 dependent. Furthermore, Tc17 cells producing IL-17 but not granzyme B are also detectable in EAE, a mouse model for multiple sclerosis. Our data point to the existence of mutually exclusive CTL and Tc17 developmental pathways in vitro and in vivo.

Details

ISSN :
00142980
Volume :
39
Database :
OpenAIRE
Journal :
European Journal of Immunology
Accession number :
edsair.doi...........11a2de55c9df21ebce536a7c27b5399f
Full Text :
https://doi.org/10.1002/eji.200939412