TY - JOUR
T1 - CD40L blockade prevents autoimmune diabetes by induction of bitypic NK/DC regulatory cells
AU - Homann, Dirk
AU - Jahreis, Angelika
AU - Wolfe, Tom
AU - Hughes, Anna
AU - Coon, Bryan
AU - Van Stipdonk, Marianne J.B.
AU - Prilliman, Kiley R.
AU - Schoenberger, Stephen P.
AU - Von Herrath, Matthias G.
N1 - Funding Information:
This work was supported by NIH grants AI51973, R01AI4451, R29 DK51091, and U-19 to M.G.v.H. D.H. was supported by JDFI Postdoctoral Fellowship 3-1999-629. A.J. was supported by fellowship BMBF-LPD9801-9 of the Deutsche Akademie der Naturforscher Leopoldina with support from the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie. S.P.S. was supported by American Cancer Society RA6 CIM 07369, M.J.B.v.S. by a fellowship from the Dutch Cancer Society, and K.R.P. by a fellowship from the Leukemia and Lymphoma Society. We thank Diana Frye for assistance with the manuscript.
PY - 2002
Y1 - 2002
N2 - Systemic treatment with antibody to CD40 ligand (aCD40L) can prevent autoimmunity and transplant rejection in several animal models and is currently under evaluation in clinical trials. While it is known that aCD40L administration inhibits expansion and effector functions of aggressive T cells, it is still unclear whether additional regulatory mechanisms are operative. Here we demonstrate that a single episode of CD40L blockade during development of the autoaggressive immune response completely prevented autoimmune disease in the RIP-LCMV mouse model for virally induced type 1 diabetes. Interestingly, protection could be transferred by a highly potent, bitypic cell population sharing phenotypic and functional properties of both natural killer (NK) and dendritic cells (DC). Furthermore, protection of prediabetic recipients was autoantigen specific and did not result in generalized immunosuppression. The origin, function, and therapeutic potential of these bitypic NK/DC regulatory cells is discussed.
AB - Systemic treatment with antibody to CD40 ligand (aCD40L) can prevent autoimmunity and transplant rejection in several animal models and is currently under evaluation in clinical trials. While it is known that aCD40L administration inhibits expansion and effector functions of aggressive T cells, it is still unclear whether additional regulatory mechanisms are operative. Here we demonstrate that a single episode of CD40L blockade during development of the autoaggressive immune response completely prevented autoimmune disease in the RIP-LCMV mouse model for virally induced type 1 diabetes. Interestingly, protection could be transferred by a highly potent, bitypic cell population sharing phenotypic and functional properties of both natural killer (NK) and dendritic cells (DC). Furthermore, protection of prediabetic recipients was autoantigen specific and did not result in generalized immunosuppression. The origin, function, and therapeutic potential of these bitypic NK/DC regulatory cells is discussed.
UR - http://www.scopus.com/inward/record.url?scp=0036201121&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(02)00290-X
DO - 10.1016/S1074-7613(02)00290-X
M3 - Article
C2 - 11911825
AN - SCOPUS:0036201121
SN - 1074-7613
VL - 16
SP - 403
EP - 415
JO - Immunity
JF - Immunity
IS - 3
ER -