Origins and functional basis of regulatory CD11c+CD8+ T cells

✍ Scribed by Dass S. Vinay; Chang H. Kim; Beom K. Choi; Byoung S. Kwon

• Book ID: 102824673
• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 651 KB
• Volume: 39
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200839057

✦ Synopsis

Abstract

Previously, we showed that CD11c defines a novel subset of CD8^+^ T cells whose in vivo activity is therapeutic for arthritis; however, the mechanisms directing their development, identity of their precursors, and basis of their effector function remain unknown. Here, we show that the novel subset develops from CD11c^surface−^CD8^+^ T cells and undergoes robust expansion in an antigen‐ and 4‐1BB (CD137)‐dependent manner. CD11c^+^CD8^+^ T cells exist in naïve mice (<3%) with limited suppressive activity. Once activated, they suppress CD4^+^ T cells in vivo and in vitro. Suppression of CD4^+^ by CD11c^+^CD8^+^ T cells is related to an increase in IDO activity induced in competent cells via the general control non‐derepressible‐2 pathway. CD11c^+^CD8^+^ T cells are refractory to the effect of IDO but constrict in a novel 1‐methyl D,L‐tryptophan‐dependent mechanism resulting in reversal of their suppressive effects. Thus, our data uncover, for the first time, the origin, development, and basis of the suppressive function of this novel CD11c^+^CD8^+^ T‐cell subpopulation that has many signature features of Treg.