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.