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 developed progressively growing intraocular tumors and displayed characteristics of immunological tolerance to SV40 T antigen. Transgenic mice failed to mount CTL responses to SV40 T antigen-bearing tumor cell lines derived from the transgenic intraocular tumors. Spleen cells from transgenic hosts were able to prevent the in vivo and in vitro generation of CTL responses by lymphocytes from normal syngeneic FVB/N mice. Adoptive transfer of spleen cells from tolerant transgenic donors temporarily inhibited the immunological rejection of SV40 T antigen-positive 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, SV40 T antigen-bearing tumor cells failed to experience immune privilege in the anterior chamber and did not elicit systemic down-regulation of delayed-type hypersensitivity responses that characteristically occur when antigens are introduced into the anterior chamber. The results indicate that within the anterior chamber of the eye, SV40 T antigen-bearing cells are perceived by the host's immune system much differently than are other categories of antigen. Thus, SV40 T antigen effectively induces self-immunological tolerance when its gene is introduced into the host's germline but fails to experience immunological privilege in the anterior chamber of the eye in normal hosts.
Ma
D
D
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas 75235.
Comerford
S
S
Bellingham
D
D
Sambrook
J
J
Gething
M J
MJ
Alizadeh
H
H
Anand
R
R
Mellon
J
J
Niederkorn
J Y
JY
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D000917:Antibody Formation; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology*; D005134:Eye Neoplasms / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic
D000952:Antigens, Polyomavirus Transforming