The findings here reveal that gain-of-function mutation of a conserved CARD11 residue, located in the coiled-coil domain recurrently mutated in B- and T-lymphomas, caused cell-autonomous accumulation of effector CD8 and CD4 T cells, and particularly of TFH, TREG and TFR cells that are critical to coordinating and regulating adaptive immune responses. The gene discussed is CD4; the disease is lymphoma.