The frequency of CD127(low )expressing CD4(+)CD25(high )T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis

BACKGROUND: CD4(+)CD25(high )regulatory T (T(Reg)) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of T(Reg )cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of T(Reg )cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation. RESULTS: We were able to confirm that HTLV-I drives activation, spontaneous IFNγ production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4(+ )T(Reg )cells (CD4(+)CD25(high )T cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4(+ )T(Reg )cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127(low )T(Reg )cells in healthy control subjects. Finally, the proportion of CD127(low )T(Reg )cells correlated inversely with HTLV-1 proviral load. CONCLUSION: Taken together, the results suggest that T(Reg )cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4(+ )T cells, in particular those expressing the CD25(high)CD127(low )phenotype. T(Reg )cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.