Considering the enrichment of IFN-γ-signature and upregulation of JAK2 in the M5 cluster of CSF myeloid cells, in parallel with increased abundance of proteins downstream of type-I and type-II IFN-signaling in chronic active MS (CXCL10 in CSF; IFIT3, EIF2AK2, MAP4K5, and STAT2 in serum), it is plausible that the CD8-TEM cells described in our data traffic to the CNS and influence resident glial cells to propagate neuroinflammation and neurodegeneration. Here, IFIT3 is linked to myeloid sarcoma.