HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) inflammatory network

Abstract

HTLV-1 associated myelopathy/ tropical spastic paraparesis (HAM/TSP) is a systemic immune-mediated inflammatory disease and tissues other than nervous can be damaged, mainly ocular, rheumatic and dermatologic. Over 90% of HTLV-1-infected individuals remain lifelong asymptomatic and this retrovirus persists indefinitely in their CD4+ T-lymphocytes. The infection is maintained due to the proliferation of lymphocytes that harbor a provirus and express HTLV-1 proteins, particularly Tax, promoting an active and selective expansion of infected T cells. High proviral load is related to disease progression, which is correlated to disequilibrium between host and virus. Cytotoxic T lymphocytes are abundant and chronically activated in asymptomatic carriers and in HAM/TSP patients. The asymptomatic carriers were shown to have a high frequency of pro-inflammatory monocytes and anti-inflammatory IL-10+CD4+ and IL-10+CD8+ T-cells, as an immunoregulatory mechanism to counterbalance the monocyte-derived TNF-alpha. A putative immunomodulatory event would be the key to control their overall immunological status. In HAM/TSP, a pro-inflammatory microenvironment is the hallmark of the immunological profile. Enhanced frequency of activated CD8+ T-cells (HLA-DR+) in combination with high CD18 surface expression has been seen. In blood and cerebrospinal fluid, increased levels of Type-1 cytokines, as interferon-(IFN)-gamma, Tumor Necrosis Factor (TNF)-alpha, Interleukin (IL)-2, and pro-inflammatory IL-6, can be found. Concerning the progression, HLA polymorphisms may influence HAM/TSP and the allele HLA-A*2 has been associated with protection. The authors showed that HAM/TSP is strongly associated with a decreased percentage of B-cells, with enhanced T/B-cell ratio and activated CD8+ T-cells. These immunological parameters have been proposed as a prognostic biomarker for HAM/TSP.