title: Genes related to antiviral activity, cell migration, and lysis are differentially expressed in CD4(+) T cells in human t cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis patients.
abstract: Human T cell leukemia virus type 1 (HTLV-1) preferentially infects CD4(+) T cells and these cells play a central role in HTLV-1 infection. In this study, we investigated the global gene expression profile of circulating CD4(+) T cells from the distinct clinical status of HTLV-1-infected individuals in regard to TAX expression levels. CD4(+) T cells were isolated from asymptomatic HTLV-1 carrier (HAC) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients in order to identify genes involved in HAM/TSP development using a microarray technique. Hierarchical clustering analysis showed that healthy control (CT) and HTLV-1-infected samples clustered separately. We also observed that the HAC and HAM/TSP groups clustered separately regardless of TAX expression. The gene expression profile of CD4(+) T cells was compared among the CT, HAC, and HAM/TSP groups. The paxillin (Pxn), chemokine (C-X-C motif ) receptor 4 (Cxcr4), interleukin 27 (IL27), and granzyme A (Gzma) genes were differentially expressed between the HAC and HAM/TSP groups, regardless of TAX expression. The perforin 1 (Prf1) and forkhead box P3 (Foxp3) genes were increased in the HAM/TSP group and presented a positive correlation to the expression of TAX and the proviral load (PVL). The frequency of CD4(+)FOXP3(+) regulatory T cells (Treg) was higher in HTLV-1-infected individuals. Foxp3 gene expression was positively correlated with cell lysis-related genes (Gzma, Gzmb, and Prf1). These findings suggest that CD4(+) T cell activity is distinct between the HAC and HAM/TSP groups.
authors.affiliation: 1 National Institute of Science and Technology in Stem Cell and Cell Therapy , Center for Cell-Based Therapy and Regional Blood Center of Ribeirão Preto, Ribeirão Preto, Brazil .
authors.forename: Mariana Tomazini
authors.initials: MT
authors.lastname: Pinto
authors.forename: Tathiane Maistro
authors.initials: TM
authors.lastname: Malta
authors.forename: Evandra Strazza
authors.initials: ES
authors.lastname: Rodrigues
authors.forename: Daniel Guariz
authors.initials: DG
authors.lastname: Pinheiro
authors.forename: Rodrigo Alexandre
authors.initials: RA
authors.lastname: Panepucci
authors.forename: Kelen Cristina Ribeiro
authors.initials: KC
authors.lastname: Malmegrim de Farias
authors.forename: Alessandra De Paula
authors.initials: Ade P
authors.lastname: Sousa
authors.forename: Osvaldo Massaiti
authors.initials: OM
authors.lastname: Takayanagui
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
authors.forename: Simone
authors.initials: S
authors.lastname: Kashima
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002353:Carrier State / Q000276:immunology*; D020869:Gene Expression Profiling; D016355:Genes, pX; D015490:HTLV-I Infections / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged
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