CD4+ T cell subsets and Tax expression in HTLV-1 associated diseases

Abstract

Human T lymphotropic virus type 1 (HTLV-1) infection displays variable clinical manifestations. These include inflammatory diseases such as HTLV-1 associated myelopathy (HAM) or immunosuppressive conditions such as Strongyloides stercoralis hyperinfection. The viral protein, Tax causes activation and proliferation of T cells. We hypothesize that the expression of Tax in T cell subsets characterizes the clinical manifestations of HTLV-1. To test this hypothesis, we measured T helper 1 effector cells and regulatory T cells (Tregs) among Tax expressing lymphocytes from peripheral blood mononuclear cells (PBMCs) of 32 HTLV-1 infected patients with HAM, with S. stercoralis co-infection or with asymptomatic infection. We observed increased ratios of Th1/Treg among Tax expressing lymphocytes in HAM patients. These data suggest that the expression of Tax among the different target cells may explain the variable presentation of HTLV-1.

Figure 1

Comparative median proportions of CD4+ T cells subsets and ratios among the clinical manifestations of human T lymphotropic virus type 1 (HTLV-1) infection (A) HAM patients presented a larger proportion of Th1 when compared to SS/HTLV-1 and asymptomatic carriers (Kruskal–Wallis: P = 0.04; Mann–Whitney test: *SS/HTLV-1 vs HAM: P = 0.04; **asymptomatic carriers vs HAM: P = 0.04) (B) HAM patients presented higher median proportions of Th1 among Tax expressing CD4+ T cells when compared to asymptomatic carriers or SS/HTLV-1 patients (Kruskal–Wallis P = 0.01; *Mann–Whitney test: P = 0.03; **Mann–Whitney test: P = 0.009) (C) The Th1/Tregs ratio among Tax expressing CD4+ was increased in HAM compared to asymptomatic infection and strongyloidiasis patients (Kruskal–Wallis P = 0.02; *Mann–Whitney test: P = 0.01; **Mann–Whitney test: P = 0.04). SS/HTLV-1: Strongyloides stercoralis and HTLV-1 co-infection, ACs: asymptomatic carriers, HAM: HTLV-1 associated myelopathy.

Figure 2

Regulatory T cell (Tregs) characterization by flow cytometry. Regulatory T cells are characterized by the expression of the transcription factor Forkhead Box p3 (Foxp3). In addition, they present a high expression of the IL-2R (CD25) and low or no expression of IL-7R (CD127). Here we show that the majority of Foxp3 cells were also CD25^high/CD127^low/neg, making Foxp3 a reliable marker for Tregs during HTLV-1 infection.