Advantages and disadvantages of and cooperation between CD8⁺ and CD4⁺ regulatory T cells

Adaptive immune responses are based on the cooperative harmony between CD4⁺ and CD8⁺ T cells. This principle applies not only to typical effector T cells but also to regulatory T cells. Studies of CD4⁺ regulatory T cells have greatly advanced after the discovery of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Treg), whereas progress in understanding the dynamics of CD8⁺ regulatory T cells has been much slower. Although several CD8⁺ regulatory T cells with different markers have been reported, these cells have not been studied as extensively as CD4⁺ Treg. Among CD8⁺ regulatory T cells, the CD8⁺CD122⁺ regulatory T cells in mice and their human counterparts, CD8⁺CXCR3⁺ cells, appear to be the most promising for further study. Following the initial discovery of CD8⁺CD122⁺ regulatory T cells, the same research group has clarified part of the molecular mechanism of these regulatory T cells and determined the important roles of these cells in certain autoimmune diseases by using experimental mouse models. In this review, we summarize the advantages and disadvantages of each CD8⁺ regulatory T cell population in comparison with CD4⁺ Treg and other CD8⁺ regulatory T cells. Furthermore, we present experimental results showing the synergistic effect of CD8⁺CD122⁺ regulatory T cells and CD4⁺ Treg and suggest that both CD4⁺ and CD8⁺ regulatory T cells be used for the treatment of immune diseases.