Here we describe a previously unknown form of inherited immunodeficiency revealed by an N-ethyl-N-nitrosourea-induced mutation called elektra. Mice homozygous for this mutation showed enhanced susceptibility to bacterial and viral infection and diminished numbers of T cells and inflammatory monocytes that failed to proliferate after infection and died via the intrinsic apoptotic pathway in response to diverse proliferative stimuli. They also had a greater proportion of T cells poised to replicate DNA, and their T cells expressed a subset of activation markers, suggestive of a semi-activated state. We positionally ascribe the elektra phenotype to a mutation in the gene encoding Schlafen-2 (Slfn2). Our findings identify a physiological role for Slfn2 in the defense against pathogens through the regulation of quiescence in T cells and monocytes.
Bibliographical noteFunding Information:
We thank O. Milstein, J.F. Purton and K. Brandl for discussions; M.B.A. Oldstone (The Scripps Research Institute) for the Armstrong strain of LCMV; and C.D. Surh (The Scripps Research Institute) for monoclonal anti-IL-7 (M25). Supported by the European Molecular Biology Organization (M.B. and P.K.), the Swiss National Science Foundation (P.K.) and the US National Institutes of Health (PO1 AI070167-01).