CD4 and Autoimmunity: The broad upregulation of a number of pro-inflammatory cytokines in PD-1−/− HSC recipients (IFN-γ, IL-13, TNF-α, IP-10, MIG, MCP-1, VEGF) (24) along with the lack of requirement for either perforin- or Fas-dependent killing pathways for autoimmunity in this model suggest that the immune pathology seen is primarily a CD4 T cell and “cytokine-storm” dependent phenomenon.