NKG2A is a marker for acquisition of regulatory function by human CD8+ T cells activated with anti-CD3 antibody

✍ Scribed by Vitaly Ablamunits; Octavian Henegariu; Paula Preston-Hurlburt; Kevan C. Herold

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 435 KB
• Volume: 41
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.201041258

✦ Synopsis

Abstract

Treatment with anti‐CD3 mAb modulates immune responses that cause type 1 diabetes and other diseases. CD8^+^ Tregs can be induced in vitro and in vivo by mAb. However, 1/3 of patients do not respond to drug therapy and in an equal proportion, anti‐CD3 mAb does not induce Tregs in vitro. The acquisition of CD8^+^ Treg activity is a function of the CD8^+^ cells and not the targets in the assay. To identify markers to differentiate responses of CD8^+^ Tregs, we analyzed genes differentially expressed in CD8^+^ T cells of non‐responders compared with responders, and found that an inhibitory receptor NKG2A (CD159a) was highly expressed in cells from all non‐responders tested. Application of a mAb agonistic to NKG2A during in vitro CD8^+^ Treg induction by anti‐CD3 prevented induction of CD8^+^ Tregs. CD8^+^ T cells that are TNFR2^+^ but NKG2A^−^ are the most potently induced Tregs. The level of NKG2A expression on resting CD8^+^ T cells inversely correlated with acquisition of regulatory function when activated. We suggest that the induction of human CD8^+^ Tregs by anti‐CD3 mAb is controlled by a negative signaling through NKG2A, and that NKG2A may serve as a negative marker of human CD8^+^ Tregs.