LFA-1 is critical for regulatory T cell homeostasis and function

Cellular adhesion molecules involved in cell-to-cell mediated suppression by Tregs are not well characterized. We found that the majority of Tregs expressed LFA-1 but most strikingly that the frequency of Tregs in LFA-1−/− mice was significantly lower (∼50%) in the spleen, lymph nodes, and Peyer's patches compared to wild type controls. The reduction in LFA-1−/− Treg cells appears due in part to a reduced capacity of LFA-1−/− CD4+CD25− cells to be induced to become Tregs in the lymph nodes. Importantly, we found that LFA-1−/− Tregs fail to suppress T cell responses in vitro and have reduced function in vivo. Treg-mediated suppression does not depend on LFA-1 interactions with ICAM-1 on the surface of responder cells. Our data demonstrate that LFA-1 plays a critical role in regulatory T cell homeostasis and function.