A Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence

We describe a new form of inherited immunodeficiency revealed by an N-ethyl-N-nitrosourea (ENU)-induced mutation called elektra. Homozygotes showed enhanced susceptibility to bacterial and viral infections, and diminished numbers of T cells and inflammatory monocytes that failed to proliferate upon infection and died via the intrinsic apoptotic pathway in response to diverse proliferative stimuli. Elektra mice exhibited an increased proportion of T cells poised to replicate DNA and their T cells expressed a subset of activation markers, suggestive of a semi-activated state. The elektra phenotype was positionally ascribed to a mutation in the gene encoding Schlafen-2 (Slfn2). Our findings reveal a physiological role for Slfn2 in the defense against pathogens through regulation of quiescence in T cells and monocytes.