TY - JOUR
T1 - FoxP3+RORγt+ T helper intermediates display suppressive function against autoimmune diabetes
AU - Tartar, Danielle M.
AU - VanMorlan, Amie M.
AU - Wan, Xiaoxiao
AU - Guloglu, F. Betul
AU - Jain, Renu
AU - Haymaker, Cara L.
AU - Ellis, Jason S.
AU - Hoeman, Christine M.
AU - Cascio, Jason A.
AU - Dhakal, Mermagya
AU - Oukka, Mohamed
AU - Zaghouani, Habib
PY - 2010/4/1
Y1 - 2010/4/1
N2 - Recently, traces of double-positive FoxP3+RORγt + T cells were identified and viewed as dual programming differentiation intermediates geared toward development intoTregulatory or Th17 cells. In this study, we report that FoxP3+RORγt+ intermediates arise in the NOD mouse T cell repertoire prior to inflammation and can be expanded with tolerogen without further differentiation. Furthermore, FoxP3+RORγt+ cells express both CD62L and membrane-bound TGFβ and use the former to traffic to the pancreas and the latter to suppress effector T cells both in vitro and in vivo. The cells perform these functions as FoxP3+RORγt+ intermediates, despite being able to terminally differentiate into either FoxP3 +RORγt- Tregulatory or FoxP3 -RORγt+ Th17 cells on polarization. These previously unrecognized observations extend plasticity to both differentiation and function and indicate that the intermediates are poised to traffic to sites of inflammation and target diverse pathogenic T cells, likely without prior conditioning by effector T cells, thus broadening efficacy against autoimmunity.
AB - Recently, traces of double-positive FoxP3+RORγt + T cells were identified and viewed as dual programming differentiation intermediates geared toward development intoTregulatory or Th17 cells. In this study, we report that FoxP3+RORγt+ intermediates arise in the NOD mouse T cell repertoire prior to inflammation and can be expanded with tolerogen without further differentiation. Furthermore, FoxP3+RORγt+ cells express both CD62L and membrane-bound TGFβ and use the former to traffic to the pancreas and the latter to suppress effector T cells both in vitro and in vivo. The cells perform these functions as FoxP3+RORγt+ intermediates, despite being able to terminally differentiate into either FoxP3 +RORγt- Tregulatory or FoxP3 -RORγt+ Th17 cells on polarization. These previously unrecognized observations extend plasticity to both differentiation and function and indicate that the intermediates are poised to traffic to sites of inflammation and target diverse pathogenic T cells, likely without prior conditioning by effector T cells, thus broadening efficacy against autoimmunity.
UR - http://www.scopus.com/inward/record.url?scp=77951643783&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0903324
DO - 10.4049/jimmunol.0903324
M3 - Article
C2 - 20181889
AN - SCOPUS:77951643783
SN - 0022-1767
VL - 184
SP - 3377
EP - 3385
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -