CD8(+)CD122(+) T-cells have been traditionally described as antigen-specific memory T-cells that respond to previously encountered antigens more quickly and vigorously than their naïve counterparts. However, mounting evidence has demonstrated that murine CD8(+)CD122(+) T-cells exhibit a central memory phenotype (CD44(high)CD62L(high)), regulate T cell homeostasis, and act as regulatory T-cells (Treg) by suppressing both autoimmune and alloimmune responses. Importantly, naturally occurring murine CD8(+)CD122(+) Tregs are more potent in immunosuppression than their CD4(+)CD25(+) counterparts. They appear to be acting in an antigen-non-specific manner. Human CD8(+)CXCR3(+) T-cells are the equivalent of murine CD8(+)CD122(+) Tregs and also exhibit central memory phenotypes. In this mini-review article, we will summarize recent progresses in their phenotypes, homeostatic expansion, antigen-specificity, roles in the suppression of alloimmune and autoimmune responses, and the mechanisms underlying their inhibitory function.