Therefore, our results indicate that NKG2D+CD4+ T cells can kill Treg cells induced to express NKG2DL by IFN-α in a NKG2D-NKG2DL-dependent manner, thereby leading to the dramatic reduction in Treg numbers in SLE and highlighting the NKG2D-NKG2DL interaction as a novel therapeutic target for SLE treatment. Here, CD4 is linked to systemic lupus erythematosus.