Proposed model integrating viral and host biomarkers for disease severity and the effect of IFN-β in HAM/TSP. Viral tax could be driving the upregulation of CD80-expressing B cells in an IFN-γ/IRF-1 [77, 78] or TNF/NF-κB [79, 80, 84] dependent manner. HBZ downregulates tax  and the NF-κB pathway , thereby possibly downregulating CD80 expression. IFN-γ-producing CD4+CD25+CCR4+Foxp3- host cells  could positively influence CD80 expression in a STAT-1/IRF-1-dependent manner. IFN-β induced downregulation of CD80 expression in B cells  could be, in part, due to its antagonistic effect on IFN-γ [100–102] as well as modulation of cytokines (IL-10 and IL-12) [105, 106] regulating IFN-γ. CD86 expression by IFN-β may be driven via STAT-1 or possibly via IL-10. HTLV-1-infected pDCs produce endogenous IFN-α , which might upregulate B cell CD86 expression in vivo. The continuous arrows and inhibition lines indicate published data, while the discontinuous lines indicate hypothetical links drawn from this study. The proinflammatory molecules/cells are in shades of brown/red, while anti-inflammatory molecules/cells are in shades of green. Proposed biomarkers for HAM/TSP are enclosed in boxes.