title: HAM/TSP-derived HTLV-1-infected T cell lines promote morphological and functional changes in human astrocytes cell lines: possible role in the enhanced T cells recruitment into Central Nervous System.
abstract: BACKGROUND
  The mechanisms through which HTLV-1 leads to and maintains damage in the central nervous system of patients undergoing HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) are still poorly understood. In recent years, increasing evidence indicates that, not only lymphocytes but also glial cells, in particular astrocytes, play a role in the pathophysiology of HAM/TSP. In this study we used a model of co-culture between human HTLV-1-infected (CIB and C91PL) and non-infected (CEM) T lymphocyte cell lines and astrocyte (U251 and U87) cell lines to mimic the in vivo T cell-astrocyte interactions.
  
  
  RESULTS
  We first observed that CIB and C91PL adhere strongly to cultured astrocytes cell lines, and that co-cultures of HTLV-1 infected and astrocyte cell lines cells resulted in rapid syncytium formation, accompanied by severe morphological alterations and increased apoptotic cell death of astrocyte cells. Additionally, cultures of astrocyte cell lines in presence of supernatants harvested from HTLV-1-infected T cell cultures resulted in significant increase in the mRNA of CCL2, CXCL1, CXCL2, CXCL3, CXCL10, IL-13, IL-8, NFKB1, TLR4, TNF, MMP8 and VCAM1, as compared with the values obtained when we applied supernatants of non-infected T- cell lines. Lastly, soluble factors secreted by cultured astrocytic cell lines primed through 1-h interaction with infected T cell lines, further enhanced migratory responses, as compared to the effect seen when supernatants from astrocytic cell lines were primed with non-infected T cell lines.
  
  
  CONCLUSIONS
  Collectively, our results show that HTLV-1 infected T lymphocyte cell lines interact strongly with astrocyte cell lines, leading to astrocyte damage and increased secretion of attracting cytokines, which in turn may participate in the further attraction of HTLV-1-infected T cells into central nervous system (CNS), thus amplifying and prolonging the immune damage of CNS.
authors.affiliation: National Institute of Health, Ministry of Health, Av. Eduardo Mondlane, 1008, Maputo, Mozambique. esamogudojr@gmail.com.|Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. esamogudojr@gmail.com.
authors.forename: Eduardo Samo
authors.initials: ES
authors.lastname: Gudo
authors.affiliation: National Cancer Institute, Rio de Janeiro, Brazil. susebarbosa@hotmail.com.
authors.forename: Suse Dayse
authors.initials: SD
authors.lastname: Silva-Barbosa
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. leandralacerda@gmail.com.
authors.forename: Leandra
authors.initials: L
authors.lastname: Linhares-Lacerda
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. mribalves@gmail.com.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ribeiro-Alves
authors.affiliation: Laboratory of Structural Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. scrf@ioc.fiocruz.br.
authors.forename: Suzana Corte
authors.initials: SC
authors.lastname: Real
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. dumith.chequer@gmail.com.
authors.forename: Dumith Chequer
authors.initials: DC
authors.lastname: Bou-Habib
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. savino.w@gmail.com.
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
mesh_terms: D001253:Astrocytes / Q000166:cytology* / Q000276:immunology; D002460:Cell Line; D002490:Central Nervous System / Q000473:pathology*; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D020869:Gene Expression Profiling; D015490:HTLV-I Infections / Q000473:pathology*; D006801:Humans; D008954:Models, Biological; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*
chemical_list: D016207:Cytokines