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

• Published in: The Journal of experimental medicine Vol. 195; no. 11; pp. 1407 - 1418
• Main Authors: Oehlen, C, Kalos, M, Cheng, LE, Shur, A C, Hong, D J, Carson, B D, Kokot, NCT, Lerner, C G, Sather, B D, Huseby, E S, Greenberg, P D
• Format: Journal Article
• Language: English
• Published: 01-06-2002
• ISSN: 0022-1007
• DOI: 10.1084/jem.20011063

CD8 super(+) 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 super(+) T cells in the periphery. Peripheral CD8 super(+) 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 super(2+) flux, ERK1/2, and Jun kinase-phosphorylation, 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 super(+) T cell tolerance.