Marked upregulation of PD‐1 on splenic CD4+ T cells with increased NFATc1 and HIF‐1α activation; PD‐1+ CD4+ T cells highly activated, secreting IFN‐γ, IL‐10, IL‐2, and IL‐4; associated with splenomegaly and severe immune modulation. The gene discussed is CD4; the disease is Splenomegaly.