T cells are responsive to the simian virus 40 large tumor antigen transgenically expressed in pancreatic islets.
The qualities of a peripheral Ag that determine whether T cells will be tolerant of or responsive to it are poorly understood. To approach this problem, we studied the T cell response in a line of transgenic mice selectively expressing an oncoprotein in the islets of Langerhans. The SV40 large tumor Ag (SV40-T) is directed to islet beta-cells in Rip1-Tag3 (RT3) mice by a hybrid insulin promoter-SV40-T construct. Ag is first detected on these cells between 10 and 12 wk after birth. RT3 mice were bred with mice expressing a transgenic rearranged TCR recognizing SV40-T in the context of the class I MHC molecule, H-2Kk. T cell response in the resultant RT3/TCR-double transgenic mice was then analyzed. T cells are fully responsive to SV40-T in RT3/TCR-transgenic mice, and T cells infiltrate the islets of both RT3 and RT3/TCR-transgenic mice. This work demonstrates that T cells may remain responsive to self-Ag expressed outside the thymus, and that this responsiveness may result in autoimmunity. The developmentally delayed expression or the oncogenic nature of SV40-T in the RT3-transgenic mice may be important in determining this T cell response.
Geiger
T
T
Section of Immunobiology, Yale University School of Medicine, New Haven, CT.
Soldevila
G
G
Flavell
R A
RA
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D015551:Autoimmunity; D015870:Gene Expression; D007108:Immune Tolerance; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D013539:Simian virus 40 / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000952:Antigens, Polyomavirus Transforming