A
peptide based on
complementarity-determining region (CDR)-1 of a monoclonal murine anti-
DNA Ab that bears the common idiotype, 16/6Id, was synthesized and characterized. The
peptide, designated pCDR1, was found to be an immunodominant
T-cell epitope in BALB/c mice. The CDR1-based
peptide was shown to be capable of inhibiting the in vivo priming of BALB/c mice immunized with the
peptide or with the whole anti-
DNA 16/6Id(+) mAbs of either mouse or human origin. We show here that administration of pCDR1 (weekly, i.v., 100 microgram/mouse) in aqueous
solution for 5 weeks starting at the time of disease induction with the human 16/6Id prevented the development of clinical manifestations of experimental
systemic lupus erythematosus (SLE). Further, 10 weekly
injections of pCDR1 to BALB/c mice with an established experimental SLE down-regulated clinical manifestations of SLE (e.g., anti-
DNA auto-Abs,
leukopenia,
proteinuria,
immune complex deposits in the kidneys) in the treated mice. Prevention of SLE induction was shown to be associated mainly with a decrease in the levels of
IL-2, INFgamma, and the proinflammatory
cytokine TNFalpha. On the other hand, the secretion of the immunosuppressive
cytokine TGFbeta was elevated. Amelioration of the clinical manifestations of an already established experimental SLE correlated with a dramatic decrease in
TNFalpha secretion, elevated levels of
TGFbeta, and
immunomodulation of the Th1 and Th2 type
cytokines to levels close to those observed in healthy mice.