Abstract
A CD30 ligand (CD30L; CD153) and its receptor, CD30, is a membrane-associated glycoprotein belonging to the TNF superfamily and TNFR superfamily. These were expressed preferentially by activated CD4+T cells. In this paper, we show that CD44lowCD62hi CD4 + T cells from CD30L-/- or CD30-/- mice exhibited impaired differentiation into Th17 cells but an increased ability to produce IL-2 after in vitro culture under Th17-polarizing conditions. Neutralization with IL-2 by anti-IL-2 mAb partly restored the ability of Th17 differentiation in CD30L-/- or CD30-/- T cells. Stimulation via CD30L by immobilized anti-CD30L mAb suppressed IL-2 production by CD30-/-CD4+ T cells, indicating that the reverse signal to CD30L is responsible for down-regulation of IL-2 production. In vivo Th17 differentiation of CD30L-/-CD4+CD45RBhigh T cells was also impaired after transfer into SCID mice, whereas CD30L +/+CD4+CD45RBhigh T cells normally differentiated into Th17 cells in CD30L-/-SCID mice. The results of these studies demonstrate that CD30L/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production.
| Original language | English |
|---|---|
| Pages (from-to) | 2222-2230 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 185 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Aug 15 2010 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
Cite this
CD30 ligand/CD30 plays a critical role in Th17 differentiation in mice. / Sun, Xun; Yamada, Hisakata; Shibata, Kensuke; Muta, Hiromi; Tani, Kenzaburo; Podack, Eckhard R.; Yoshikai, Yasunobu.
In: Journal of Immunology, Vol. 185, No. 4, 15.08.2010, p. 2222-2230.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CD30 ligand/CD30 plays a critical role in Th17 differentiation in mice
AU - Sun, Xun
AU - Yamada, Hisakata
AU - Shibata, Kensuke
AU - Muta, Hiromi
AU - Tani, Kenzaburo
AU - Podack, Eckhard R.
AU - Yoshikai, Yasunobu
PY - 2010/8/15
Y1 - 2010/8/15
N2 - A CD30 ligand (CD30L; CD153) and its receptor, CD30, is a membrane-associated glycoprotein belonging to the TNF superfamily and TNFR superfamily. These were expressed preferentially by activated CD4+T cells. In this paper, we show that CD44lowCD62hi CD4 + T cells from CD30L-/- or CD30-/- mice exhibited impaired differentiation into Th17 cells but an increased ability to produce IL-2 after in vitro culture under Th17-polarizing conditions. Neutralization with IL-2 by anti-IL-2 mAb partly restored the ability of Th17 differentiation in CD30L-/- or CD30-/- T cells. Stimulation via CD30L by immobilized anti-CD30L mAb suppressed IL-2 production by CD30-/-CD4+ T cells, indicating that the reverse signal to CD30L is responsible for down-regulation of IL-2 production. In vivo Th17 differentiation of CD30L-/-CD4+CD45RBhigh T cells was also impaired after transfer into SCID mice, whereas CD30L +/+CD4+CD45RBhigh T cells normally differentiated into Th17 cells in CD30L-/-SCID mice. The results of these studies demonstrate that CD30L/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production.
AB - A CD30 ligand (CD30L; CD153) and its receptor, CD30, is a membrane-associated glycoprotein belonging to the TNF superfamily and TNFR superfamily. These were expressed preferentially by activated CD4+T cells. In this paper, we show that CD44lowCD62hi CD4 + T cells from CD30L-/- or CD30-/- mice exhibited impaired differentiation into Th17 cells but an increased ability to produce IL-2 after in vitro culture under Th17-polarizing conditions. Neutralization with IL-2 by anti-IL-2 mAb partly restored the ability of Th17 differentiation in CD30L-/- or CD30-/- T cells. Stimulation via CD30L by immobilized anti-CD30L mAb suppressed IL-2 production by CD30-/-CD4+ T cells, indicating that the reverse signal to CD30L is responsible for down-regulation of IL-2 production. In vivo Th17 differentiation of CD30L-/-CD4+CD45RBhigh T cells was also impaired after transfer into SCID mice, whereas CD30L +/+CD4+CD45RBhigh T cells normally differentiated into Th17 cells in CD30L-/-SCID mice. The results of these studies demonstrate that CD30L/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production.
UR - http://www.scopus.com/inward/record.url?scp=77956897477&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956897477&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1000024
DO - 10.4049/jimmunol.1000024
M3 - Article
C2 - 20639486
AN - SCOPUS:77956897477
VL - 185
SP - 2222
EP - 2230
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -