Treatment of induced murine SLE with a peptide based on the CDR3 of an anti-DNA antibody reverses the pattern of pathogenic cytokines.
A peptide based on the complementarity determining region (CDR) 3 of a pathogenic anti-DNA monoclonal antibody that bears the 16/6 idiotype (Id) was shown previously to be a dominant T-cell epitope in experimental SLE, and to be capable of inhibiting SLE-associated responses. When injected, concomitant with active immunization with the pathogenic human anti-DNA, 16/6 Id+ mAb, pCDR3 inhibited the proliferation of LN-derived T cells stimulated in vitro with the 16/6 Id mAb. The inhibition of the specific proliferative responses could be reversed by the addition of exogenous IL-2 to the cultures. Analysis of secreted cytokine profile in supernatants of these cultures demonstrated that pCDR3 treatment reduced significantly the levels of both IL-2 and IFN-gamma that were elevated further in cells of the 16/6 Id-immunized mice. The CDR3-based peptide was shown here to immunomodulate in vivo experimental SLE, induced by the human anti-DNA 16/6 Id+ antibody. The beneficial effects of pCDR3 on the clinical manifestations of SLE were associated with downregulation of the Th1-type (IL-2, IFN-gamma) and proinflammatory (TNF-alpha) cytokines, whereas the immunosuppressive cytokine TGF-beta was up regulated.
Brosh
Naama
N
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Zinger
Heidy
H
Mozes
Edna
E
D000818:Animals; D000974:Antibodies, Antinuclear / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D022801:Complementarity Determining Regions / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D051379:Mice
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007130:Immunoglobulin Idiotypes; D004247:DNA