TY - JOUR
T1 - The role of CD28 and CTLA4 in the function and homeostasis of CD4 +CD25+ regulatory T cells
AU - Boden, Elisa
AU - Tang, Qizhi
AU - Bour-Jordan, Helene
AU - Bluestone, Jeffrey A.
AU - Bach,
AU - Hafler,
AU - Banchereau,
PY - 2003
Y1 - 2003
N2 - CD4+CD25+ T cells regulate a variety of autoimmune and alloimmune responses including the development of autoimmune diabetes in non-obese diabetic (NOD) mice. We have examined the role of CD28/CTLA4/B7 interactions in the expansion and survival of CD4+CD25+ regulatory T cells (Treg) in this setting. CD28/ B7 interactions are essential in the development of Treg in the thymus and for their survival in the periphery. The CD28-mediated homeostasis of these cells is independent of IL2, OX40, CD40L, and survival factor Bcl-XL. In addition, analysis of Treg from CTLA4-deficient mice suggests that CTLA4 expression is not required for their development or function. However, non-activating anti-CTLA4 antibodies blocked the suppressor activity of regulatory cells in vitro. Thus, clinical application of co-stimulatory blockade using agents such as CTLA4Ig in the treatment of autoimmune disease may result in complicated outcomes.
AB - CD4+CD25+ T cells regulate a variety of autoimmune and alloimmune responses including the development of autoimmune diabetes in non-obese diabetic (NOD) mice. We have examined the role of CD28/CTLA4/B7 interactions in the expansion and survival of CD4+CD25+ regulatory T cells (Treg) in this setting. CD28/ B7 interactions are essential in the development of Treg in the thymus and for their survival in the periphery. The CD28-mediated homeostasis of these cells is independent of IL2, OX40, CD40L, and survival factor Bcl-XL. In addition, analysis of Treg from CTLA4-deficient mice suggests that CTLA4 expression is not required for their development or function. However, non-activating anti-CTLA4 antibodies blocked the suppressor activity of regulatory cells in vitro. Thus, clinical application of co-stimulatory blockade using agents such as CTLA4Ig in the treatment of autoimmune disease may result in complicated outcomes.
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M3 - Review article
C2 - 14609212
AN - SCOPUS:2142649142
SN - 1528-2511
VL - 252
SP - 55
EP - 66
JO - Novartis Foundation Symposium
JF - Novartis Foundation Symposium
ER -