More MS news articles for June 2002

CD8(+) T Cell Tolerance to a Tumor-associated Antigen Is Maintained at the Level of Expansion Rather than Effector Function

J Exp Med 2002 Jun 3;195(11):1407-18
Ohlen C, Kalos M, Cheng LE, Shur AC, Hong DJ, Carson BD, Kokot NC, Lerner CG, Sather BD, Huseby ES, Greenberg PD.
Department of Immunology, University of Washington, Seattle, WA 98195. Department of Medicine/Division of Oncology, University of Washington, Seattle, WA 98195. Fred Hutchinson Cancer Research Center, Seattle, WA 98109.

CD8(+) T cell tolerance to self-proteins prevents autoimmunity but represents an obstacle to generating T cell responses to tumor-associated antigens.

We have made a T cell receptor (TCR) transgenic mouse specific for a tumor antigen and crossed TCR-TG mice to transgenic mice expressing the tumor antigen in hepatocytes (gag-TG).

TCRxgag mice showed no signs of autoimmunity despite persistence of high avidity transgenic CD8(+) T cells in the periphery.

Peripheral CD8(+) T cells expressed phenotypic markers consistent with antigen encounter in vivo and had upregulated the antiapoptotic molecule Bcl-2.

TCRxgag cells failed to proliferate in response to antigen but demonstrated cytolytic activity and the ability to produce interferon gamma.

This split tolerance was accompanied by inhibition of Ca(2+) flux, ERK1/2, and Jun kinasephosphorylation, and a block in both interleukin 2 production and response to exogenous interleukin 2.

The data suggest that proliferation and expression of specific effector functions characteristic of reactive cells are not necessarily linked in CD8(+) T cell tolerance.