Format

Send to

Choose Destination
Eur J Immunol. 2009 Jul;39(7):1716-25. doi: 10.1002/eji.200939412.

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

Author information

1
Institute for Medical Microbiology and Hygiene, University of Marburg, Germany. huberma@med.uni-marburg.de

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.

PMID:
19544308
DOI:
10.1002/eji.200939412
[Indexed for MEDLINE]
Free full text

Publication type, MeSH terms, Substances

Publication type

MeSH terms

Substances

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center