title: Altered expression of degranulation-related genes in CD8+ T cells in human T lymphotropic virus type I infection.
abstract: Human T lymphotropic virus type I (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD8+ T cells may contribute to the protection or development of HAM/TSP. In this study we used SAGE methodology to screen for differentially expressed genes in CD8+ T cells isolated from HTLV-1 asymptomatic carriers (HAC) and from HAM/TSP patients to identify genes involved in HAM/TSP development. SAGE analysis was conducted by pooling samples according to clinical status. The comparison of gene expression profiles between HAC and HAM/TSP libraries identified 285 differentially expressed tags. We focus on cytotoxicity and cytokine-related genes due to their potential biological role in HTLV-1 infection. Our results showed that patients with HAM/TSP have high expression levels of degranulation-related genes, namely GZMH and PRF1, and of the cytoskeletal adaptor PXN. We found that GZMB and ZAP70 were overexpressed in HTLV-infected patients compared to the noninfected group. We also detected that CCL5 was higher in the HAM/TSP group compared to the HAC and CT groups. Our findings showed that CD8+ T cells of HAM/TSP patients have an inflammatory and active profile. PXN and ZAP70 overexpression in HTLV-1-infected patients was described for the first time here and reinforces this concept. However, although active and abundant, CD8+ T cells are not able to completely eliminate infected cells and prevent the development of HAM/TSP and, moreover, these cells might contribute to the pathogenesis of the disease by migrating to the central nervous system (CNS). These results should be further tested with biological functional assays to increase our understanding on the role of these molecules in the development of HTLV-1-related diseases.
authors.affiliation: National Institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell Therapy and Regional Blood Center, Blood Center of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Tathiane M
authors.initials: TM
authors.lastname: Malta
authors.forename: Israel T
authors.initials: IT
authors.lastname: Silva
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pinheiro
authors.forename: Anemarie R D
authors.initials: AR
authors.lastname: Santos
authors.forename: Mariana T
authors.initials: MT
authors.lastname: Pinto
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Panepucci
authors.forename: Osvaldo M
authors.initials: OM
authors.lastname: Takayanagui
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Dimas T
authors.initials: DT
authors.lastname: Covas
authors.forename: Simone
authors.initials: S
authors.lastname: Kashima
mesh_terms: D000328:Adult; D000368:Aged; D058345:Asymptomatic Infections; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology / Q000821:virology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral / Q000235:genetics / Q000502:physiology; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D015490:HTLV-I Infections / Q000276:immunology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; C510468:PRF1 protein, human; C496061:PXN protein, human; D051419:Paxillin; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C509213:GZMB protein, human; C069434:GZMH protein, human; D053804:Granzymes