CAPACITY OF SIMIAN-VIRUS-40 T-ANTIGEN TO INDUCE SELF-TOLERANCE BUT NOT IMMUNOLOGICAL PRIVILEGE IN THE ANTERIOR-CHAMBER OF THE EYE

Transgenic mice bearing the simian virus 40 (SV40) large T oncogene de veloped progressively growing intraocular tumors and displayed charact eristics of immunological tolerance to SV40 T antigen. Transgenic mice failed to mount CTL responses to SV40 T antigen-bearing tumor cell li nes derived from the transgenic intraocular tumors. Spleen cells from transgenic hosts were able to prevent the in vivo and in vitro generat ion of CTL responses by lymphocytes from normal syngeneic FVB/N mice. Adoptive transfer of spleen cells from tolerant transgenic donors temp orarily inhibited the immunological rejection of SV40 T antigen-positi ve tumor cells transplanted to normal syngeneic FVB/N recipients. Thus , introduction of SV40 transforming sequences into the mouse germline induced tolerance to SV40 T antigen. However, in normal FVB/N mice, SV 40 T antigen-bearing tumor cells failed to experience immune privilege in the anterior chamber and did not elicit systemic down-regulation o f delayed-type hypersensitivity responses that characteristically occu r when antigens are introduced into the anterior chamber. The results indicate that within the anterior chamber of the eye, SV40 T antigen-b earing cells are perceived by the host's immune system much differentl y than are other categories of antigen. Thus, SV40 T antigen effective ly induces self-immunological tolerance when its gene is introduced in to the host's germline but fails to experience immunological privilege in the anterior chamber of the eye in normal hosts.