|Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
Activins, members of the transforming growth factor-b(TGF-β) superfamily, are pluripotent growth and differentiation factors. In many biological systems, activins have overlapping biological activities with TGF-β partly due to the fact that activins and TGF-bs utilize the same proteins (Smad2 and/or Smad3) in signal transduction. The expression and function of activin in the immune system are not yet fully characterized, in contrast to the extensive knowledge of TGF-β's functions. It inhibits the proliferation and differentiation into effector cells, and induces the apoptosis in T cells. We investigated the regulatory expression of activin A in CD4^+ helper T cells. Our results revealed that activin A is produced by CD4^+T cells in response to their activation. In recent years, CD4+CD25+ regulatory T cells have emerged as a unique population of suppressor T cells that produce high levels of TGF-β that is involved in maintaining peripheral immune tolerance. We determined if activin A is produced in CD4^+CD25^+T cells and acts as a suppressor of T cell functions. Activin expression was not detected in CD4^+CD25^+ regulatory T cells even when they were stimulated with anti-CD3 and anti-CD28 mAbs, although TGF-b1 was highly expressed. Addition of activin A, follistatin or anti-activin mAb to the culture barely affected the in vitro suppression of T cell proliferation by CD4^+CD25^+ regulatory T cells. In contrast, TGF-β1 but not activin A efficientiy inhibited T-cell proliferation in a dose-dependent manner. Thus, the function ofactivin is distinct from that of TGF-β at least on the proliferation of CD4^+ T cells.