Systemic lupus erythematosus (SLE) can be induced in mice by immunizing them with a monoclonal human anti-DNA Ab that expresses a major Id, designated 16/6Id. In addition, a peptide based on the sequence of the CDR 1 (hCDR1) of the 16/6Id ameliorated the clinical manifestations of SLE in experimental models. In this study we examined the elects of treating mice with human complementary-determining region 1 (hCDR1) on the subsequent chemotaxis of T cells derived from 16/6Id-primed mice. First we demonstrated elevated levels of stromal cell-derived factor-1α (SDF-1α) in the sera of SLE-afflicted mice and in the sera and lymphoid tissues of 16/6Id-immunized BALB/c mice shortly after the immunization. We then found that administration of hCDR1 to 16/6Id-immunized mice specifically down-regulated SDF1α-induced T cell chemotaxis through fibronectin and collagen type I. This was accompanied by diminished SDF1-α-induced T cell adhesion and ERK phosphorylation. Treatment with hCDR1 up-regulated TGF-β secretion, which, in turn, inhibited the marine T cell adhesion to and chemotaxis through fibronectin as well as their ERK phosphorylation. Thus, the secretion of TGF-β after treatment of 16/6Id-immunized mice with hCDR1 plays an important role in the down-regulation of SDF-1α-mediated T cell activation and the interactions with extracellular matrix moieties observed to the present study.