Global expression profiling of peripheral Qa-1–restricted CD8αα+TCRαβ+ regulatory T cells reveals innate-like features: Implications for immune-regulatory repertoire

Among peripheral regulatory T cells, CD8+ T cells also play an important role in the maintenance of immune homeostasis. A subset of CD8+ Treg that express αβ T cell receptor (TCR) and CD8αα homodimers can recognize TCR-derived peptides in the context of the class Ib MHC molecule Qa-1. To gain a better understanding of the nature and phenotype of CD8αα+TCRαβ+ Treg, a global gene expression profiling using microarray, real-time quantitative polymerase chain reaction, and flow-cytometric analysis was performed using functional Treg clones and lines. The study findings show that CD8+ Treg shared gene profile expressed by innate-like lymphocytes, including murine intraepithelial lymphocytes and thymic CD8αα+TCRαβ+ T-cell populations. In addition, this subset displays differential expression of several key regulatory molecules, including CD200. CD8αα+ Treg expressed higher levels of a number of natural killer cell–related receptors and molecules belonging to the TNF superfamily. Collectively, peripheral class Ib-reactive CD8αα+TCRαβ+ T cells represent a unique regulatory population different from class Ia major histocompatibility complex–restricted conventional T cells. These studies have important implications for the regulatory mechanisms mediated by the CD8+ Treg population in general.