Editors' ChoiceImmunology

Immunology: Ignorance or Tolerance in T-cell--Mediated Autoimmunity

Science's STKE  09 Nov 1999:
Vol. 1999, Issue 7, pp. tw4
DOI: 10.1126/stke.1999.7.tw4

Autoimmunity to antigens in pancreatic islets contributes to type 1 diabetes and thus control of this process has been of particular interest. Both tolerance (a process in which reactive CD8+ T cells are removed by apoptosis) or ignorance (a process in which autoreactive T cells do not respond to antigens in the islet) can occur. However, it has been unclear why some antigens induce one process but other antigens produce the other. Kurts et al. studied the effects of ovalbumin expressed in the islets of transgenic mice. They found that the concentration of the antigen determined whether tolerance or ignorance was observed. In low concentrations, ovalbumin was not detected by CD8+ T cells. However, if larger amounts of ovalbumin were expressed, cross-presentation (in which CD8+ T cells are activated in the lymph nodes by presentation of antigen from non-lymphoid tissues) occurred and resulted in deletion of CD8+ T cells reactive with ovalbumin. These two alternative mechanisms may allow an organism to be protected from autoimmunity in response to low or high concentrations of antigen.

Kurts, C., Sutherland, R.M., Davey, G., Li, M., Lew, A.M., Blanas, E., Carbone, F.R., Miller, J.F.A.P., and Heath, W.R. (1999) CD8 T cell ignorance or tolerance to islet antigens depends on antigen dose Proc. Natl. Acad. Sci. U.S.A. 96: 12703-12707. [Abstract] [Full Text]