The C587R mutation in the hematopoietic lineage causes an interferon-signature in lymphocytes. (A) Representative barcode enrichment plots of IFN signatures in C587R/+ CD8-naive T cells. (B) Mixed BM chimeras were set up as shown for Figure 4C. Representative FACS plot showing chimerism in the CD4-naive compartment: WT CD45.1⁺CD45.2⁺ “competitor cells” coexisting with either WT (top panel) or C587R-mutant CD45.2⁺ “test cells” (bottom panel). (C) The IFN signature is hematopoietic in origin and the result of paracrine signaling. Quantitative PCR results show that the IFN-stimulated genes Stat1 and Gbp2 are upregulated in “competitor cells” when in presence of C587R/+ mutant “test cells.” Each point represents the value obtained from CD4 T cells sorted an individual mouse. (D) The IFN signature is dependent on IFNγ signaling. The IFN signature was maintained in C587R mutant CD4-naive T cells purified from mice lacking the Ifnar1 gene but not the Ifnγ gene. Each point represents the value obtained from CD4 T cell sorted an individual mouse. The loss of Ifnar1 (E) or Ifnγ (F) did not restore neither lymphopenia nor thrombocytopenia. (E) Circles and triangles represent cell numbers for an individual mouse. Data show mean with SD. *P < .05; **P < .01; ***P < .001; and ****P < .0001.