4.1 Article

T cell receptor signaling pathway is overexpressed in CD4+ T cells from HAM/TSP individuals

Journal

BRAZILIAN JOURNAL OF INFECTIOUS DISEASES
Volume 19, Issue 6, Pages 578-584

Publisher

ELSEVIER BRAZIL
DOI: 10.1016/j.bjid.2015.07.008

Keywords

HTLV-1; HAM/TSP; CD4(+) T cell activation; Gene expression

Funding

  1. Fundacao Hemocentro de Ribeirao Preto (FUNDHERP)
  2. Centro Regional de Hemoterapia de Ribeirao Preto (CRH)
  3. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
  4. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
  5. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

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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 CD3 epsilon), lymphocyte-specific protein tyrosine kinase LCK), vav 1 guanine nucleotide exchange factor VAV1), and zeta-chain TCR) associated protein kinase 70 kDa ZAP70) on T lymphocytes of HTLV-1-infected individuals and compared to healthy uninfected individuals (CT). We observed that CD3 epsilon, 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 CD3 epsilon, 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 CD3 epsilon, 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. (C) 2015 Elsevier Editora Ltda. All rights reserved.

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