Upon CD46 co-activation, CD46 is cleaved by a metalloproteinase (MMP), resulting in the release of soluble CD46 in the milieu. sCD46 is likely to retain its binding function, suggesting a potential ability to further regulate T cell activation or neighboring cells. CD46 Cyt1 cytoplasmic tail is then cleaved by the presenilin/γ-secretase concomitantly with an increased in Cyt2 expression. This provides an “on” signal for T cells, resulting in proliferation, IL-10 secretion, and increased CD25 expression. Cleavage of Cyt2 by the P/γS terminates T cell activation by inhibiting T cell proliferation, decreasing IFNγ production and CD25 expression.