NUCLEAR APPEARANCE OF A FACTOR THAT BINDS THE CD28 RESPONSE ELEMENT WITHIN THE INTERLEUKIN-2 ENHANCER CORRELATES WITH INTERLEUKIN-2 PRODUCTION

Activation of T lymphocytes requires the combined signaling of the T c ell receptor and costimulatory molecules such as CD28. The ability of T cells to produce interleukin-2 (IL-2) is a critical control point in T lymphocyte activation. The IL-2 enhancer contains a functional moti f named CD28 response element (CD28RE) that serves a role as a target for mitogenic T cell activation signals. The CD28RE sequence reveals s imilarity to the consensus kappa B binding motif. Here we demonstrate that CD28RE binds an inducible protein with a molecular mass of approx imately 35 kDa called nuclear factor of mitogenic-activated T cells (N F-MATp35) that is clearly different from the known NF-kappa B/Rel fami ly members. Induction of NF-MATp35 was shown to depend on de novo prot ein synthesis and was restricted to T cells that received a mitogenic combination of T cell stimuli, not necessarily including CD28 signalin g. Nonmitogenic T cell stimulation did not result in appearance of NF- MATp35. These results indicate that mitogenic combinations of T cell a ctivation signals are integrated at the level of NF-MATp35 induction. Similar to its effect on IL-2 production, cyclosporin A inhibited the induction of NF-MATp35. Taken together, these data demonstrate that th e nuclear appearance of NF-MATp35 shows excellent correlation with IL- 2 production, which is a unique characteristic among nuclear factors i mplicated in the control of IL-2 gene expression.