CD 2‐mediated regulation of peripheral CD 4 + CD 25 + regulatory T ‐cell apoptosis accompanied by down‐regulation of B im

Summary Extensive studies on CD 4 +   CD 25 + regulatory T ( T reg) cells suggest that they are important in regulating immune responses. However, mechanisms of peripheral T reg cell homeostasis are unknown. We found that stromal cells isolated from secondary lymphoid organs such as spleen and lymph nodes could support the survival of T reg cells. This was dependent on CD 2 engagement and a direct interaction between Treg cells and stromal cells. In the presence of stromal cells, B im, a pro‐apoptotic factor, was partially decreased in T reg cells. This effect could be inhibited by anti‐ CD 2 blocking antibodies, indicating that stimulation through CD 2 on T reg cells regulates B im expression, which may be relevant to T reg cell apoptosis. Therefore, T reg cell interactions with stromal cells through CD 2 may be essential for T reg cell survival. Surprisingly, the expression of CD 2 ligands on stromal cells was not detected. Hence, it is not clear how CD 2 on T reg cells contributes to a direct interaction with the stromal cells and participates in survival support for T reg cells. Taken together, CD 2 stimuli were mandatory for T reg cell survival with reduced B im expression, but CD 2 may not function as a direct receptor for molecules on stromal cells.