Background:  Toll-like receptor-2 (TLR2) has been described as a co-stimulatory receptor on CD8⁺ T cells, decreasing the threshold for antigen-induced T-cell activation. On the other hand, engagement of TLR2 on CD4⁺CD25⁺ regulatory T cells (Treg) enhances their function. TLR2 is present on surface of dendritic cells (DC), mostly myeloid DC (mDC), which is essential for T-cell priming. Since the exact mechanism involved in pathogenesis of human T-cell lymphotropic virus-associated myelopathy (HTLV-I)/tropical spastic paraparesis (HAM/TSP) is not clearly understood, we investigated the expression of TLR2 on different cell types in HTLV-I-infected asymptomatic subjects (HTLV-I⁺) and HAM/TSP patients.

Methods:  We enrolled 9 health volunteers (controls), 7 HTLV-I-infected asymptomatic volunteers (HTLV-I⁺), and 9 patients with HAM/TSP. Using flow cytometry, we evaluated expression of TLR2 on the surface of T cells and DC subsets. CD4⁺ and CD8⁺ T cells were isolated using magnetic columns. Proviral load was quantified by real time polymerase chain reaction (RT-PCR) in CD4- and CD8-enriched conditions. Nonparametric analyzes were performed, significance threshold was defined at p <0.05; data are reported as median (IQR).

Results:  We observed that the percentage of TLR2^high was significantly increased (p <0.05) in several cell types from HAM/TSP, including total T cells (TLR2^high on controls: 1.05, IQR 0.53 to 1.65; HTLV-I⁺:  0.61, IQR 0.48 to 1.05; HAM/TSP:  1.37, IQR 1.22 to 2.54), CD8⁺ T cells (TLR2^high on controls:  0.5800, IQR 0.3350 to 0.8800; HTLV-I⁺:  0.4500, IQR 0.3100 to 0.7500; HAM/TSP:  1.310, IQR 0.8600 to 2.970), and CD4^–CD8^– T cells (TLR2^high on controls:  1.780, IQR 1.165 to 2.455; HTLV-I⁺:  1.030, IQR 0.7400 to 1.680; HAM/TSP:  7.450, IQR 4.540 to 11.70), whereas CD4⁺ and CD4⁺CD8⁺ T cells presented only a trend to higher expression. Nevertheless, the expression of TLR2 on CD4⁺TLR2⁺ T cells was inversely correlated with proviral load in CD4 enriched peripheral blood mononuclear cells (PBMC) of HAM/TSP patients (r = –0.785714, p <0.05), which suggest its role in viral replication control.

Conclusions:  For the first time, we described a marked up-regulation of TLR2 on several T-cell subtypes from HAM/TSP patients, constituting a candidate marker for either progression or severity of such disease. The level of TLR2 expression on CD4⁺ T cells may be able to control viral replication. One should explore the TLR2 pathway to better understand the immunopathogenesis of HAM/TSP, with potential therapeutic implications.