Figure 3 In vitro effects of natalizumab on proliferation and interferon-γ secretion of purified CD4⁺ T cells

(A, B) CD4⁺ T cells were isolated from peripheral blood mononuclear cells from healthy donors and stimulated with plate-bound anti-CD3 (1 μg/mL) in the presence of physiologic concentrations of natalizumab or isotype matched control antibody for 72 hours. The figure shows percent reduction (mean ± SD) in [³H]-thymidine incorporation (A) and interferon-γ secretion (B) in cultures with natalizumab compared to control antibody. (C–F) CD4⁺ T cells were labeled with 5 μM CFSE, stimulated with anti-CD3 for 5 days, and stained with CD4 and 7-AAD to measure proliferation and activation-induced cell-death (AICD). The figure shows percent CD4⁺ cells with at least one cell division in cultures treated with 15 μg/mL natalizumab (C) or control immunoglobulin (D). AICD was calculated as percent dead cells stained with 7-AAD in the population of dividing cells (as gated in C and D) in cultures treated with 15 μg/mL natalizumab (E) or control immunoglobulin G (F). The figure shows one representative donor of 10.