The frequency of CD127low expressing CD4+CD25high 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

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Abstract
Background: CD4+CD25highregulatory T (TReg) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of TRegcell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of TRegcells 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+TRegcells (CD4+CD25highT cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4+TRegcells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127lowTRegcells in healthy control subjects. Finally, the proportion of CD127lowTRegcells correlated inversely with HTLV-1 proviral load.Conclusion: Taken together, the results suggest that TRegcells 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 CD25highCD127lowphenotype. TRegcells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.

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