A Th17-like developmental process leads to CD8(+) Tc17 cells with reduced cytotoxic activity.
Standard
A Th17-like developmental process leads to CD8(+) Tc17 cells with reduced cytotoxic activity. / Huber, Magdalena; Heink, Sylvia; Grothe, Henrike; Guralnik, Anna; Reinhard, Katharina; Elflein, Karin; Hünig, Thomas; Mittrücker, Hans Willi; Brüstle, Anne; Kamradt, Thomas; Lohoff, Michael.
In: EUR J IMMUNOL, Vol. 39, No. 7, 7, 2009, p. 1716-1725.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - A Th17-like developmental process leads to CD8(+) Tc17 cells with reduced cytotoxic activity.
AU - Huber, Magdalena
AU - Heink, Sylvia
AU - Grothe, Henrike
AU - Guralnik, Anna
AU - Reinhard, Katharina
AU - Elflein, Karin
AU - Hünig, Thomas
AU - Mittrücker, Hans Willi
AU - Brüstle, Anne
AU - Kamradt, Thomas
AU - Lohoff, Michael
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 39
SP - 1716
EP - 1725
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 7
M1 - 7
ER -
