Thus, while our primary hypothesis that anti–PD-1 CAR T cells could selectively abrogate TFH cells containing SIV turned out to be correct and achievable, the associated “off-target” immunodeficiency indicates that additional genetic engineering is required to increase anti–PD-1 CAR specificity toward PD-1+ CD4 T cells alone and to include safety switches to abrogate anti–PD-1 CAR T cells in vivo to minimize the long-term effects of CAR T cell persistence. The gene discussed is CD4; the disease is immunodeficiency disease.