Recombinant Human Anti-CD25 Antibody (Daclizumab) (CAT#: PABX-029)

Figure 1 Inhibitory effect of daclizumab on T cell survival in in vitro cultures appears to be mediated by NK cells and requires NK–T cell contact.

(A) PBMC or NK-depleted PBMC (by CD56 microbeads) from the same samples were stained with CFSE, polyclonally activated (plate-bound CD3/CD28) for 72 h in the presence/absence of daclizumab, washed and reseeded in T cell media enriched for IL-7 and IL-15 (with or without daclizumab), and followed for long-term survival. Corresponding flow cytometry profiles of equivalent proportions of cultures (CFSE proliferation together with intracellular cytokine staining for IL-2) at day 8 after stimulation are depicted from a representative patient from samples before and during daclizumab therapy.

Bielekova, B., Catalfamo, M., Reichert-Scrivner, S., Packer, A., Cerna, M., Waldmann, T. A., ... & Martin, R. (2006). Regulatory CD56bright natural killer cells mediate immunomodulatory effects of IL-2Rα-targeted therapy (daclizumab) in multiple sclerosis. Proceedings of the National Academy of Sciences, 103(15), 5941-5946.

Figure 2 NK cells are cytotoxic toward activated autologous T cells.

(C) Cytotoxicity of purified CD56ᵈⁱᵐ and CD56ᵇʳⁱᵍʰᵗ NK cells from MS patients undergoing daclizumab therapy on autologous T cells. T cells were left unstimulated or were stimulated with PMA/ionomycin for 12 h. Daclizumab (10 μg/ml) was added to the assays as indicated. Inhibition of NK subset cytotoxicity by anti-CD16 Ab (1 μg/ml) is depicted in red. Each plot corresponds to a representative experiment from two to five subjects.

Bielekova, B., Catalfamo, M., Reichert-Scrivner, S., Packer, A., Cerna, M., Waldmann, T. A., ... & Martin, R. (2006). Regulatory CD56bright natural killer cells mediate immunomodulatory effects of IL-2Rα-targeted therapy (daclizumab) in multiple sclerosis. Proceedings of the National Academy of Sciences, 103(15), 5941-5946.

Figure 3 Effect of daclizumab on T cell and NK cell proliferation.

(B) IL-2 dependence of the daclizumab effect on CD4+ T cell proliferation. Effect of daclizumab on T cell proliferation was assessed by titrating different doses of exogenous IL-2 to resting or suboptimally stimulated (anti-CD3, 5 ng/ml) CFSE-stained PBMC. Proliferation was assessed 72 h after stimulation by thymidine incorporation (cpm) and by CFSE dilution (no. of mitoses per 100 gated cells). Daclizumab inhibited proliferation of CD4+ T cells only (B Center), and this could be completely overcome by high doses of IL-2.

Bielekova, B., Catalfamo, M., Reichert-Scrivner, S., Packer, A., Cerna, M., Waldmann, T. A., ... & Martin, R. (2006). Regulatory CD56bright natural killer cells mediate immunomodulatory effects of IL-2Rα-targeted therapy (daclizumab) in multiple sclerosis. Proceedings of the National Academy of Sciences, 103(15), 5941-5946.