Abrogation of PLP139-151–induced EAE by hmTAP is associated with inhibition of encephalitogenic T cells. Systemic administration of hmTAP intraperitoneally (a) and intravenously (b) suppresses PLP139-151–induced EAE. At the times indicated (arrows), SJL/J mice injected for EAE with PLP139-151 (150 μg) in CFA supplemented with 200 μg Mt, received 200 μg of PLP139-151, shPLP215, shMOG/E, or hmTAP in 500 μl PBS or PBS alone. I and M indicate incidence of disease and mortality in the group, respectively. (c) Inhibition of encephalitogenic T cells in hmTAP-treated mice is accompanied by a shift to noninflammatory cytokine secretion. Left panel: SJL/J mice primed with PLP139-151/CFA were injected intravenously on days 2, 4, 6, and 8 with hmTAP or OVA (∼100 μg) in 500 μl PBS. On day 9, isolated LNCs were analyzed for their proliferative response to PLP139-151 and shPLP215, as well as to purified protein derivative (PPD) of Mt (0.5 μg/200 μl culture) as a control for immunocompetence. Each histogram represents the mean stimulation index (SI) of triplicate cultures; the percentage of inhibition of proliferation by LNCs from hmTAP-treated mice as compared with LNCs from OVA-treated mice is indicated. Background cpm ± SD was 537 ± 100 and 432 ± 68 for LNCs isolated from mice injected with OVA and hmTAP, respectively. Right panel: Spleen cells from the hmTAP- or OVA-treated mice were incubated (5 × 106 spleen cells/ml) with PLP139-151 (20 μg/ml); IL-2 and IFN-γ were assayed by ELISA on supernatants collected after 12 hours in culture and IL-4 and IL-10 on supernatants collected after 72 hours in culture.