Targeted antibody treatment rapidly, transiently, and safely depletes T cells with no long-term detriment to T-cell function. (A) Short-term depletion. Anti-CD3 mAb administered after birth at 20 DPC depletes PB T cells to 0% of all CD45⁺ cells within 12 hours of administration. (B) Quantitative T-cell recovery. All T-cell populations recover to baseline frequency within 4 weeks of antibody treatment. (C) Weight gain. The treated animals demonstrated normal weight gain, despite antibody depletion. (D) In vivo MLR. After quantitative recovery, T cells proliferate normally when presented with a nonself MHC. (E) Maternal TCD. Anti-CD3 mAb administered to the fetus before birth at 16 DPC did not deplete T cells in the maternal blood, which remained at frequencies equal to that observed after fetal saline injection. Fetal injection with anti-CD3 mAb resulted in neonatal T-cell depletion measured at birth (F) without detriment to fetal survival to birth (G) or birth weight (H). ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001, ∗∗∗∗P < 0.0001. ns, not significant.