TY - JOUR
T1 - CTLA-4 modulates the differentiation of inducible foxp3+treg cells but IL-10 mediates their function in experimental autoimmune encephalomyelitis
AU - Verhagen, Johan
AU - Gabryšová, Leona
AU - Shepard, Ella R.
AU - Wraith, David C.
PY - 2014/9/19
Y1 - 2014/9/19
N2 - In vitro induced Foxp3+ T regulatory (iTreg) cells form a novel and promising target for therapeutic tolerance induction. However, the potential of these cells as a target for the treatment of various immune diseases, as well as the factors involved in their development and function, remain debated. Here, we demonstrate in a myelin basic protein (MBP)-specific murine model of CNS autoimmune disease that adoptive transfer of antigen-specific iTreg cells ameliorates disease progression. Moreover, we show that the co-stimulatory molecule CTLA-4 mediates in vitro differentiation of iTreg cells. Finally, we demonstrate that the secreted, immunosuppressive cytokine IL-10 controls the ability of antigen-specific iTreg cells to suppress autoimmune disease. Overall, we conclude that antigen-specific iTreg cells, which depend on various immune regulatory molecules for their differentiation and function, represent a major target for effective immunotherapy of autoimmune disease.
AB - In vitro induced Foxp3+ T regulatory (iTreg) cells form a novel and promising target for therapeutic tolerance induction. However, the potential of these cells as a target for the treatment of various immune diseases, as well as the factors involved in their development and function, remain debated. Here, we demonstrate in a myelin basic protein (MBP)-specific murine model of CNS autoimmune disease that adoptive transfer of antigen-specific iTreg cells ameliorates disease progression. Moreover, we show that the co-stimulatory molecule CTLA-4 mediates in vitro differentiation of iTreg cells. Finally, we demonstrate that the secreted, immunosuppressive cytokine IL-10 controls the ability of antigen-specific iTreg cells to suppress autoimmune disease. Overall, we conclude that antigen-specific iTreg cells, which depend on various immune regulatory molecules for their differentiation and function, represent a major target for effective immunotherapy of autoimmune disease.
UR - http://www.scopus.com/inward/record.url?scp=84907198008&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0108023
DO - 10.1371/journal.pone.0108023
M3 - Article (Academic Journal)
C2 - 25238105
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e108023
ER -