Revival of CD8+ Treg–mediated suppression

Despite their first recognition almost 40 years ago, CD8 + ‘suppressor' T cells remain poorly characterized. Recent studies of these lymphocytes, now popularly referred to as regulatory CD8 + T cells (CD8 + Tregs), have helped clarify their important role in the regulation of autoimmune disease. Here, we review progress related to the identification, phenotype and function of CD8 + Tregs. We also focus on a newly described subset, CD8αα + TCRαβ + Tregs, which in mice recognize a T-cell receptor–derived peptide in the context of the class Ib major histocompatibility complex molecule Qa-1. These Tregs target only activated T cells and complement the suppression provided by CD4 + Foxp3 + Tregs. Investigations leading to the detailed identification, expansion, maintenance and function of CD8αα + Tregs should result in new therapeutic strategies for human inflammatory diseases.