T cells from patients with systemic lupus erythematosus are characterized by decreased expression of CD3ζ-chain and increased expression of FcRγ-chain, which becomes part of the CD3 complex and contributes to aberrant signaling. Elf-1 enhances the expression of CD3ζ, whereas it suppresses the expression of FcRγ gene and lupus T cells have decreased amounts of DNA-binding 98 kDa form of Elf-1. We show that the aberrantly increased PP2A in lupus T cells dephosphorylates Elf-1 at Thr-231. Dephosphorylation results in limited expression and binding of the 98 kDa Elf-1 form to the CD3ζ and FcRγ promoters. Suppression of the expression of the PP2A leads to increased expression of CD3ζ and decreased expression of FcRγ genes and correction of the early signaling response. Therefore, PP2A serves as a central determinant of abnormal T cell function in human lupus and may represent an appropriate treatment target.