Lymphopenia-driven CD8(+) T cells are resistant to antigen-induced tolerance in NOD.scid mice

作者：Long Brian; Wong Carmen P; Wang Yaming; Tisch Roland^*

来源：European Journal of Immunology, 2006, 36(8): 2003-2012.

DOI：10.1002/eji.200535717

• autoimmunity
• diabetes
• T cells

T cells undergoing lymphopenia-driven proliferation acquire effector and memory properties that can be pathogenic. Indeed, generalized lymphopenia is associated with a variety of autoimmune diseases such as type 1 diabetes. The current study was carried out to determine how CD8(+) T cells undergoing acute lymphopenic expansion respond to antigen under tolerizing conditions in vivo. Adoptive transfer of diabetes by TCR-transgenic CD8(+) T cells was enhanced following treatment of NOD. scid recipients with a high dose of soluble peptide. Furthermore, whereas TCR-transgenic CD8(+) T cells underwent clonal deletion and failed to differentiate into CTL in peptide-treated lymphoreplete recipient mice,. TCR-transgenic CD8(+) T cells in a lymphopenic environment were resistant to clonal deletion, and CTL differentiation was enhanced by a high dose of soluble peptide. Moreover, peptide treatment had distinct effects on expression of the anti-apoptotic protein Bcl-X-L in TCR-transgenic CD8(+) T cells under lymphopenic versus lymphoreplete conditions. These results demonstrate that CD8(+) T cells undergoing lymphopenia-driven expansion in NOD. scid recipients are resistant to antigen-induced tolerance, and readily differentiate into CTL upon stimulation with a high dose of soluble peptide.

• 出版日期2006-8