The activation of CD40-CD40L costimulatory signal channel plays a necessary role in T cellmediated immune response. Activation of CD40 on antigen presenting cells by CD40L which expressed on Tlymphocytes, while contributing to the pro-in? ammatory response necessary for eradication of infection, accounts for the pathology in autoimmunity. Meanwhile, there is evidence that CD40 is also expressed on T-lymphocytes and can act as a costimulatory molecule. Further dissection of the exact nature and role of CD40 in T cell activation could lead the way to novel therapeutics for diseases which include organ-graft refection, autoimmune diseases,tumor, and inflammation.