HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) inflammatory network.
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.
Goncalves
Denise U
DU
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
Proietti
Fernando A
FA
Barbosa-Stancioli
Edel F
EF
Martins
Marina L
ML
Ribas
João G
JG
Martins-Filho
Olindo A
OA
Teixeira-Carvalho
Andrea
A
Peruhype-Magalhães
Vanessa
V
Carneiro-Proietti
Anna B
AB
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
D016207:Cytokines; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma