title: T cell receptor signaling pathway is overexpressed in CD4(+) T cells from HAM/TSP individuals.
abstract: Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus related to the chronic neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4(+) T cells activation appears to play a key role on HTLV-1 infection. Here we investigated the expression of genes associated to T cell activation CD3e molecule, epsilon (CD3ɛ), lymphocyte-specific protein tyrosine kinase (LCK), vav 1 guanine nucleotide exchange factor (VAV1), and zeta-chain (TCR) associated protein kinase 70kDa (ZAP70) on T lymphocytes of HTLV-1-infected individuals and compared to healthy uninfected individuals (CT). We observed that CD3ɛ, LCK, ZAP70, and VAV1 gene expression were increased in CD4(+) T cells from HAM/TSP group compared to HTLV-1 asymptomatic patients (HAC). Moreover, ZAP70 and VAV1 were also upregulated in HAM/TSP compared to CT group. We detected a positive correlation among all these genes. We also observed that CD3ɛ, LCK, and VAV1 genes had a positive correlation with the proviral load (PVL) and Tax expression. These results suggest that PVL and Tax protein could drive CD3ɛ, LCK, and VAV1 gene expression in CD4(+) T cells, and these genes function on a synchronized way on the CD4(+) T cell activation. The elucidation of the mechanisms underlying T cell receptor signaling pathway is of considerable interest and might lead to new insights into the mechanism of HAM/TSP.
authors.affiliation: Instituto Nacional de Ciências e Tecnologia em Células-Tronco e Terapia Celular, Centro de Terapia Celular e Centro Regional de Hemoterapia de Ribeirão Preto, Ribeirão Preto, SP, Brazil; Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Mariana Tomazini
authors.initials: MT
authors.lastname: Pinto
authors.affiliation: Instituto Nacional de Ciências e Tecnologia em Células-Tronco e Terapia Celular, Centro de Terapia Celular e Centro Regional de Hemoterapia de Ribeirão Preto, Ribeirão Preto, SP, Brazil.
authors.forename: Tathiane Maistro
authors.initials: TM
authors.lastname: Malta
authors.affiliation: Instituto Nacional de Ciências e Tecnologia em Células-Tronco e Terapia Celular, Centro de Terapia Celular e Centro Regional de Hemoterapia de Ribeirão Preto, Ribeirão Preto, SP, Brazil.
authors.forename: Evandra Strazza
authors.initials: ES
authors.lastname: Rodrigues
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Osvaldo Massaiti
authors.initials: OM
authors.lastname: Takayanagui
authors.affiliation: Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Japan.
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Instituto Nacional de Ciências e Tecnologia em Células-Tronco e Terapia Celular, Centro de Terapia Celular e Centro Regional de Hemoterapia de Ribeirão Preto, Ribeirão Preto, SP, Brazil; Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
authors.affiliation: Instituto Nacional de Ciências e Tecnologia em Células-Tronco e Terapia Celular, Centro de Terapia Celular e Centro Regional de Hemoterapia de Ribeirão Preto, Ribeirão Preto, SP, Brazil; Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: skashima@hemocentro.fmrp.usp.br.
authors.forename: Simone
authors.initials: S
authors.lastname: Kashima
mesh_terms: D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000235:genetics / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism; D019562:Viral Load; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D017252:CD3 Complex; C115335:CD3E protein, human; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; C496618:VAV1 protein, human; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human
keywords: CD4(+) T cell activation; Gene expression; HAM/TSP; HTLV-1