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Humoral and cell-mediated immune responses to epidermal growth factor in the rabbit.

Epidermal growth factor (EGF), which has been shown to stimulate epidermal proliferation and keratinization and to induce regeneration of rabbit corneal epithelium, was studied for its immunogenic potential in rabbits. Mouse-derived EGF was administered topically, subconjunctivally, intrastromally, and systemically. Systemic immunization was done both with and without complete Freund's adjuvant (CFA). EGF-stimulated cultures of lymphocytes from peripheral blood, spleen, and lymph nodes of all immunized animals were tested for cell-mediated immunity (CMI) to EGF. All experimental animals demonstrated CMI as determined by either classic positive delayed skin tests or by in vitro production of migration inhibitory factors, regardless of the route of sensitization. Only animals immunized systemically with EGF and CFA produced high-titered specific anti-EGF antibody, and only this group showed ocular reactions after subsequent topical challenge of EGF. These results suggest that antibody to EGF is the major cause for ocular inflammatory reactions observed subsequent to topical EGF challenge of a sensitized animal.