title: 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.
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde, Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Brazil. deniseg@medicina.ufmg.br
authors.forename: Denise U
authors.initials: DU
authors.lastname: Goncalves
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Proietti
authors.forename: Edel F
authors.initials: EF
authors.lastname: Barbosa-Stancioli
authors.forename: Marina L
authors.initials: ML
authors.lastname: Martins
authors.forename: João G
authors.initials: JG
authors.lastname: Ribas
authors.forename: Olindo A
authors.initials: OA
authors.lastname: Martins-Filho
authors.forename: Andrea
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.forename: Vanessa
authors.initials: V
authors.lastname: Peruhype-Magalhães
authors.forename: Anna B
authors.initials: AB
authors.lastname: Carneiro-Proietti
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000821:virology; D007371:Interferon-gamma / Q000276:immunology; D015493:Paraparesis, Tropical Spastic / Q000276:immunology* / Q000821:virology; D011110:Polymorphism, Genetic; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma