CD4+CD25-LAG-3+ T cells in mouse and human.

We have recently reported a murine novel regulatory T cell population, CD4(+)CD25(-)LAG-3(+) regulatory T cells (Tregs). Microarray analysis revealed that CD4(+)CD25(-)LAG-3(+) Tregs had a unique mRNA expression profile that was different from the conventional CD4(+)CD25(+) regulatory T cells. In particular, CD4(+)CD25(-)LAG-3(+) Tregs characteristically expressed early growth response gene 2 (Egr-2) that was reported to be associated with the induction of anergy. CD4(+)CD25(-)LAG-3(+) Tregs produced high-amount of IL-10 in response to TCR stimulation and showed immunosuppressive activity in vitro and in vivo. Retroviral gene transfer of Eg-2 converted naïve CD4(+) T cells into IL-10-secreting and LAG-3-expressing T cells, and Egr-2 transduced CD4(+) T cells exhibited antigen-specific immunosuppressive capacity in vivo. On the basis of these observations, we have attempted to identify a human counterpart of murine CD4(+)CD25(-)LAG-3(+) Tregs in human. CD4(+)CD25(-)LAG-3(+) T cells were found in human in similar pattern as murine CD4(+)CD25(-)LAG-3(+) Tregs. In the quantitative PCR, human CD4(+)CD25(-)LAG-3(+) T cells expressed high levels of IL-10. From the microarray analysis, we found the close similarity between human CD4(+)CD25(-)LAG-3(+) T cells and murine CD4(+)CD25(-)LAG-3(+) Tregs. Therefore, human CD4(+)CD25(-)LAG-3(+) T cells might be a human counterpart of murine CD4(+)CD25(-)LAG-3(+) Tregs.