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Down-Regulation of Stromal Cell-Derived Factor-1-Induced T Cell Chemotaxis by a Peptide Based on the Complementarity-Determining Region 1 of an Anti-DNA Autoantibody via Up-Regulation of TGF- Secretion¹

Uri Sela^*,, Rami Hershkoviz, Liora Cahalon^*, Ofer Lider^* and Edna Mozes^2,*

^* Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; and Assaf-Harofeh Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Zerifin, Tel-Aviv, Israel

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 effects 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-1 (SDF-1) 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 SDF1-induced T cell chemotaxis through fibronectin and collagen type I. This was accompanied by diminished SDF1--induced T cell adhesion and ERK phosphorylation. Treatment with hCDR1 up-regulated TGF- secretion, which, in turn, inhibited the murine T cell adhesion to and chemotaxis through fibronectin as well as their ERK phosphorylation. Thus, the secretion of TGF- after treatment of 16/6Id-immunized mice with hCDR1 plays an important role in the down-regulation of SDF-1-mediated T cell activation and the interactions with extracellular matrix moieties observed in the present study.

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