Background:  Adult T-cell leukemia (ATL) and human T-lymphotrophic virus-1 (HTLV-I)-associated myelopathy/tropical spastic paresis (HAM/TSP) are most important HTLV-I-associated diseases. Although both of them are related to high proviral load, host HTLV-I-specific T cells are seen frequently on HAM/TSP, however, a weak immune response are characteristic of ATL. Moreover, the incidence of ATL is higher among men, but HAM/TSP is more common and has worse clinical progression in women than in men, without a satisfactory explanation for this phenomenon. The aim of this study was to evaluate parameters of acquired and innate immunology of HTLV-I-infected asymptomatic patients, correlated with proviral load in a sex-based analysis.

Methods:  We allocated 26 volunteers into 4 groups:  healthy men (HM) and women (HW), and asymptomatic HTLV-I-infected men (MH-I⁺) and women (WH-I⁺). Using flow cytometry, we evaluated subpopulations of T cells, dendritic cells (DC) subsets, and expression of toll-like receptor (TLR)-2 on surface and TLR-9 intracellularly in those cells populations. Total peripheral blood mononuclear cells (PBMC) was fractioned on CD4- and CD8-enriched conditions using magnetic columns. Proviral load was quantified using real time polymerase chain reaction (RT-PCR). Analyses were performed with nonparametric tests and significance threshold was set at p <0.05. Values are expressed in median *IQR).

Results:  There were no statistical difference in CD3, CD4, CD8, or proviral load between parried groups. Proportion of TLR2⁺mDC was very similar between HW and HM, but it was lower on WH⁺ than MH⁺ (85.00 [80.80 to 86.85], 91.60 [87.15 to 92.55], respectively; p = 0.0317). TLR9⁺pDC subset was greater on HM (39.90 [21.20 to 88.20]) than HW (p >0.05), but pronounced higher on MH-I⁺ vs WH-I⁺ (52.80 [50.30 to 77.15], 44.10 [25.35 to 56.30], respectively; p = 0.0556). Percentage of CD4⁺TLR2⁺ T cells was smaller on HW than HM (2.805 [1.055 to 4.200], 4.965 [2.620 to 5.975], respectively; p >0.05), but it was accentuated between MH-I⁺ and WH-I⁺ (4.930 [3.455 to 6.255], 2.000 [1.100 to 3.460], respectively; p = 0.048). CD8⁺TLR2⁺ T cells were higher on HM than HW (4.235 [2.310 to 5.645], 2.420 [0.9650 to 2.770], respectively; p = 0.0426), similar to MH-I⁺ vs WH-I⁺ (3.790 [3.655 to 5.735], 1.920 [1.040 to 2.980], respectively; p = 0.0177). There was difference on proportion of CD4⁺CD8⁺TLR2⁺ T cells among MH-I⁺ and WH-I⁺ (18.30 [14.55 to 20.50], 4.720 [2.720 to 11.20], respectively; p = 0.048), but not between HM vs HW (p >0.05).

Conclusions:  Sex-related difference of immune response anti-HTLV-I probably is a feature of immunopathogenesis of HAM/TSP and ATL.