Vaccination with a recombinant vaccinia virus encoding a "self" antigen induces autoimmune vitiligo and tumor cell destruction in mice: Requirement for CD4(+) T lymphocytes

Many human and mouse tumor antigens are normal, nonmutated tissue different iation antigens, Consequently, immunization with these "self" antigens coul d induce autoimmunity. When we tried to induce immune responses to five mou se melanocyte differentiation antigens, gp100? MART-1, tyrosinase, and tyro sinase-related proteins (TRP) 1 and TRP-2, we observed striking depigmentat ion and melanocyte destruction only in the skin of mice inoculated with a v accinia virus encoding mouse TRP-1, These mice rejected a lethal challenge of B16 melanoma, indicating the immune response against TRP-1 could destroy both normal and malignant melanocytes. Cytotoxic T lymphocytes specific fo r TRP-1 could not be detected in depigmented mice, but high titers of Ige a nti-TRP-l antibodies were present, Experiments with knockout mice revealed an absolute dependence on major histocompatibility complex class II, but no t major histocompatibility complex class I, for the induction of both vitil igo and tumor protection. Together, these results suggest that the delibera te induction of self-reactivity using a recombinant viral vector can lead t o tumor destruction, and that in this model, CD4(+) T lymphocytes are an in tegral part of this process. Vaccine strategies targeting tissue differenti ation antigens may be valuable in canters arising from nonessential cells a nd organs such as melanocytes, prostate, testis, breast, and ovary.