Poster Sessions

Imm-12

Qianc Chen

Q. Chen, E. Shevach

Engagement of TLR2 promotes mouse regulatory T cell survival

Toll-like receptors (TLRs) are a class of conserved pattern recognition receptors that are used by the innate immune system to defense host. Recent studies have demonstrated that TLRs are expressed on T cells and may play a novel role in adaptive immunity. Foxp3+ Treg cells are critical for the maintenance of peripheral T cell tolerance and the prevention of autoimmune diseases. Some studies have claimed that engagement of TLR2 on mouse Tregs reversed their suppressive function. We have used Foxp3-GFP knock-in mice to examine the expression and function of TLR2 on Tregs. TLR2 mRNA could only be detected in Tregs upon TCR activation. Addition of the synthetic TLR2 agonist, Pam3CSK4, enhances Treg proliferation following TCR stimulation in the presence of IL-2. Thus, TLR2 functions as a co-stimulatory molecule on Tregs capable of lowering their threshold for CD3-mediated activation. In contrast to previous studies, we do not observe an altered suppressive function of Tregs. More importantly, TLR2 ligation prevents Treg death in vitro by up-regulating anti-apoptotic Bcl-xL protein. Therefore, TLR2 can function as a novel co-stimulatory molecule by potentiating Treg survival and may be considered as a target for modulating of Treg function in vivo in autoimmunity.