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Background  Human strongyloidiasis varies from a chronic but limited infection in normal hosts to hyperinfection in patients treated with corticosteroids or with HTLV-1 co-infection. Regulatory T cells dampen immune responses to infections. How human strongyloidiasis is controlled and how HTLV-1 infection affects this control are not clear. We hypothesize that HTLV-1 leads to dissemination of  Strongyloides stercoralis  infection by augmenting regulatory T cell numbers, which in turn down regulate the immune response to the parasite.    Objective  To measure peripheral blood T regulatory cells and  Strongyloides stercoralis  larval antigen-specific cytokine responses in strongyloidiasis patients with or without HTLV-1 co-infection.    Methods  Peripheral blood mononuclear cells (PBMCs) were isolated from newly diagnosed strongyloidiasis patients with or without HTLV-1 co-infection. Regulatory T cells were characterized by flow cytometry using intracellular staining for CD4, CD25 and FoxP3. PBMCs were also cultured with and without  Strongyloides  larval antigens. Supernatants were analyzed for IL-5 production.    Results  Patients with HTLV-1 and  Strongyloides  co-infection had higher parasite burdens. Eosinophil counts were decreased in the HTLV-1 and  Strongyloides  co-infected subjects compared to strongyloidiasis-only patients (70.0 vs. 502.5 cells/mm 3 , p = 0.09, Mann-Whitney test). The proportion of regulatory T cells was increased in HTLV-1 positive subjects co-infected with strongyloidiasis compared to patients with only strongyloidiasis or asymptomatic HTLV-1 carriers (median = 17.9% vs. 4.3% vs. 5.9 p<0.05, One-way ANOVA).  Strongyloides  antigen-specific IL-5 responses were reduced in strongyloidiasis/HTLV-1 co-infected patients (5.0 vs. 187.5 pg/ml, p = 0.03, Mann-Whitney test). Reduced IL-5 responses and eosinophil counts were inversely correlated to the number of CD4+CD25+FoxP3+ cells.    Conclusions  Regulatory T cell counts are increased in patients with HTLV-1 and  Strongyloides stercoralis  co-infection and correlate with both low circulating eosinophil counts and reduced antigen-driven IL-5 production. These findings suggest a role for regulatory T cells in susceptibility to  Strongyloides  hyperinfection.

Regulatory T Cell Expansion in HTLV-1 and Strongyloidiasis Co-infection Is Associated with Reduced IL-5 Responses to Strongyloides stercoralis Antigen