Clenoliximab and
keliximab are monkey/human chimeric
monoclonal antibodies (mAbs) of the
immunoglobulin G4 (
IgG4) and
IgG1 isotypes, respectively, that recognize the same
epitope on human CD4. The two mAbs possess identical idiotypes and exhibit equal affinities for CD4. Upon administration of these mAbs to mice that express a human CD4 transgene, but not mouse CD4 (HuCD4/Tg mice),
clenoliximab and
keliximab exhibited similar kinetics of binding to CD4, and induced the same degree of CD4 modulation from the cell surface, although only
keliximab mediated CD4+ T-cell depletion. Epicutaneous sensitization and challenge of HuCD4/Tg mice with the
hapten oxazolone resulted in a
contact sensitivity response characterized by tissue swelling, and the presence of
interferon-gamma (IFN-gamma) and
interleukin-4 (IL-4) in the local tissue. Administration of a single 2-mg dose of either
clenoliximab or
keliximab to HuCD4/Tg mice prior to sensitization significantly reduced post-challenge tissue swelling, and levels of IFN-gamma and
IL-4, indicating that CD4+ T-cell depletion is not required for anti-CD4 mAb-mediated inhibition of
contact sensitivity. Administration of either mAb prior to challenge failed to inhibit the
contact sensitivity response, indicating differential sensitivity of the afferent and efferent phases of the response to inhibition by CD4-specific mAbs. Collectively, these data indicate that CD4 functions as a positive regulatory molecule in the
contact sensitivity response.