Inhibition of NF-κB leads to the modulation of immune activation in HAM/TSP. PBMCs from subjects with HAM/TSP were placed in short-term (20 hours) culture and analyzed for the expression of CD25, CD69, and phosphorylated STAT5 (pSTAT5) by FACS analysis. (A) Representative FACS histograms (left panels) showing CD25 and CD69 expression (blue lines) in healthy donor (HD) PBMCs after 20 hours of culture. Shaded histograms are isotype control staining. Representative FACS histograms (right panels) showing CD25 and CD69 expression (blue lines) in untreated PBMCs from a HAM/TSP subject after 20 hours of culture. Green lines indicate CD25 and CD69 expression in HAM/TSP PBMCs treated with PBS-1086 (10μM). Shaded histograms are isotype control staining. (B) The mean (± SD) expression of CD25 and CD69 in untreated, DMSO, regioisomer PBS-1143 (10μM)–, DHMEQ (10μM)–, or PBS-1086 (10μM)–treated PBMCs from HAM/TSP subjects (n = 5). **P < .01, ANOVA and Dunnett posttest. (C) Representative FACS histograms showing STAT5 activation (pSTAT5) in cultured PBMCs from a healthy donor (HD, left), in untreated PBMCs from a subject with HAM/TSP (center), and in HAM/TSP PBMCs treated with the NF-κB inhibitor PBS-1086 (10μM, right). (D) representative FACS histogram showing STAT5 activation (pSTAT5) in HAM/TSP PBMCs in the presence of antibodies against the IL-2Rα (anti-Tac) and the IL-2/IL-15Rβ (Mik-β1): (1) anti-Tac (5 μg/mL) + Mik-β1 (5 μg/mL), (2) Mik-β1 (10 μg/mL), (3) anti-Tac (10 μg/mL), or (4) untreated and (5) isotype control antibody staining. (E) The mean (±SD) T-cell STAT5 activation (pSTAT5 + CD3⁺) in untreated, msIgG2a (10 μg/mL)–, anti-Tac (10 μg/mL)–, Mik-β1 (10 μg/mL)–, and anti-Tac (5 μg/mL) + Mik-β1 (5 μg/mL)–treated HAM/TSP PBMCs (n = 4). *P < .05, Kruskal-Wallis, Dunn posttest. (F) The mean (±SD) frequency of pSTAT5⁺ cells in cultured (20 hours) HAM/TSP PBMCs (n = 3) as a function of inhibitor concentration for PBS-1086 and control regioisomer PBS-1143.