TY - JOUR
T1 - Reciprocal expression of TRAIL and CD95L in Th1 and Th2 cells
T2 - Role of apoptosis in T helper subset differentiation
AU - Zhang, X. R.
AU - Zhang, L. Y.
AU - Devadas, S.
AU - Li, L.
AU - Keegan, A. D.
AU - Shi, Y. F.
N1 - Funding Information:
We thank Dr. Sidney Pestka and Ms. Jennifer Solomon for their comments on this manuscript, Dr. Xi Yang for his advice on immunization schedule, Dr. Laurie Glimcher for T cell clones and Teresa Hawley for cell sorting. This work was supported in part by USPHS grant AI43384 (YFS), AI50222 (YFS), NSBRI-IIH-00208 (YFS), AI45662 (ADK), and CA77415 (ADK). YFS is also an adjunet faculty member of Shanghai International Cancer Institute, 800 Xiang Yin Road, Shanghai, China 200433
PY - 2003/2/1
Y1 - 2003/2/1
N2 - Upon activation, naïve T helper cells can differentiate into two major distinct subsets, T helper 1 (Th1) and T helper 2 (Th2), as defined by their effector functions and cytokine secretion patterns. Cytokine milieu and costimulatory molecules have been shown to play an essential role in determining T helper differentiation. However, it is still unclear how the effects of signals of costimulatory molecules and cytokines are exerted during T helper differentiation. We show evidence suggesting that while cytokine signals initiate the differentiation program, the selective action of death effectors determines the end point balance of differentiating T helper subsets. We examined the expression of TNF-related apoptosis-inducing ligand (TRAIL) and CD95L in cloned and in vitro differentiated Th1 and Th2 cells. We found that activation-induced expression of TRAIL is exclusively observed in Th2 clones and primary T helper cells differentiated under the Th2 condition, while the expression of CD95L is mainly in Th1 cells. Furthermore, these two subsets exhibit distinct susceptibilities to TRAIL- and CD95L-mediated apoptosis. Th2 cells are more resistant to either TRAIL- or CD95L-induced apoptosis than Th1 cells. More importantly, both Th1 and Th2 cells could induce apoptosis in labeled Th1 but not Th2 cells. Blocking TRAIL and CD95L significantly enhance IFN-γ production in vitro. Likewise, young MRL/MpJ-lpr/lpr mice also showed more Th1 response to ovalbumin immunization as compared to MRL/MpJ+/+. Therefore, apoptosis mediated by CD95L and TRAIL is critical in determining the fate of differentiating T helper cells.
AB - Upon activation, naïve T helper cells can differentiate into two major distinct subsets, T helper 1 (Th1) and T helper 2 (Th2), as defined by their effector functions and cytokine secretion patterns. Cytokine milieu and costimulatory molecules have been shown to play an essential role in determining T helper differentiation. However, it is still unclear how the effects of signals of costimulatory molecules and cytokines are exerted during T helper differentiation. We show evidence suggesting that while cytokine signals initiate the differentiation program, the selective action of death effectors determines the end point balance of differentiating T helper subsets. We examined the expression of TNF-related apoptosis-inducing ligand (TRAIL) and CD95L in cloned and in vitro differentiated Th1 and Th2 cells. We found that activation-induced expression of TRAIL is exclusively observed in Th2 clones and primary T helper cells differentiated under the Th2 condition, while the expression of CD95L is mainly in Th1 cells. Furthermore, these two subsets exhibit distinct susceptibilities to TRAIL- and CD95L-mediated apoptosis. Th2 cells are more resistant to either TRAIL- or CD95L-induced apoptosis than Th1 cells. More importantly, both Th1 and Th2 cells could induce apoptosis in labeled Th1 but not Th2 cells. Blocking TRAIL and CD95L significantly enhance IFN-γ production in vitro. Likewise, young MRL/MpJ-lpr/lpr mice also showed more Th1 response to ovalbumin immunization as compared to MRL/MpJ+/+. Therefore, apoptosis mediated by CD95L and TRAIL is critical in determining the fate of differentiating T helper cells.
KW - Apoptosis
KW - CD95 ligand
KW - T helper cell type 1
KW - T helper cell type 2
KW - TRAIL
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U2 - 10.1038/sj.cdd.4401138
DO - 10.1038/sj.cdd.4401138
M3 - Article
C2 - 12700648
AN - SCOPUS:0038702580
SN - 1350-9047
VL - 10
SP - 203
EP - 210
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 2
ER -