TY - JOUR
T1 - Mechanistic assessment of PD-1H coinhibitory receptor-induced T cell tolerance to allogeneic antigens
AU - Flies, Dallas B.
AU - Higuchi, Tomoe
AU - Chen, Lieping
PY - 2015/6/1
Y1 - 2015/6/1
N2 - PD-1H is a recently identified cell surface coinhibitory molecule of the B7/CD28 immune modulatory gene family. We showed previously that single injection of a PD-1H agonistic mAb protected mice from graft-versus-host disease (GVHD). In this study, we report two distinct mechanisms operate in PD-1H-induced T cell tolerance. First, signaling via PD-1H coinhibitory receptor potently arrests alloreactive donor T cells from activation and expansion in the initiation phase. Second, donor regulatory T cells are subsequently expanded to maintain long-term tolerance and GVHD suppression. Our study reveals the crucial function of PD- 1H as a coinhibitory receptor on alloreactive T cells and its function in the regulation of T cell tolerance. Therefore, PD-1H may be a target for the modulation of alloreactive T cells in GVHD and transplantation.
AB - PD-1H is a recently identified cell surface coinhibitory molecule of the B7/CD28 immune modulatory gene family. We showed previously that single injection of a PD-1H agonistic mAb protected mice from graft-versus-host disease (GVHD). In this study, we report two distinct mechanisms operate in PD-1H-induced T cell tolerance. First, signaling via PD-1H coinhibitory receptor potently arrests alloreactive donor T cells from activation and expansion in the initiation phase. Second, donor regulatory T cells are subsequently expanded to maintain long-term tolerance and GVHD suppression. Our study reveals the crucial function of PD- 1H as a coinhibitory receptor on alloreactive T cells and its function in the regulation of T cell tolerance. Therefore, PD-1H may be a target for the modulation of alloreactive T cells in GVHD and transplantation.
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U2 - 10.4049/jimmunol.1402648
DO - 10.4049/jimmunol.1402648
M3 - Article
C2 - 25917101
AN - SCOPUS:84929650544
SN - 0022-1767
VL - 194
SP - 5294
EP - 5304
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -