Leukocyte function associated antigen-1 (LFA-1) plays a critical role in regulating T cell function.The activation of LFA-1 is strictly regulated and changes in LFA-1 affinity for ligand are important mechanisms for regulation.The control of LFA-1 activation is critical for regulating immune responses.We found that high affinity LFA-1 regulates T cell activation and proliferation.In addition,we demonstrated that locking LFA-1 in low affinity state with lovastatin can reduce GVHD mortality and morbidity in a mouse BMT model.Furthermore,we investigated the molecular mechanisms of LFA-1 in modulating CTL functions.We found that the activation of LFA-1 directly enhances Erkl/2 signal pathway,thus decreasing T cell activation threshold by promoting IL-2 production and proliferation.Thus,the affinity regulation of LFA-1 is essential for the T cell activation; locking LFA-1 in the "low affinity" state will prevent GVHD; LFA-1 regulates the activation threshold and effector function of CTL by providing the co-stimulatory signal.Our longterm goal is to elucidate the regulatory mechanisms controlling T cell activation in autoimmunity and tumor immunity.Based on our data,LFA-1 activation is important in T cell mediated immune responses.It is necessary to further determine and dissect the mechanisms,that will improve the understanding of the molecular basis ofT cell activation,and provide a scientific basis for the development of better therapies.