title: The frequency of CD127low expressing CD4+CD25high T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis.
abstract: BACKGROUND
  CD4+CD25high regulatory T (TReg) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of TReg cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of TReg cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation.
  
  
  RESULTS
  We were able to confirm that HTLV-I drives activation, spontaneous IFNgamma production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4+ TReg cells (CD4+CD25high T cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4+ TReg cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127low TReg cells in healthy control subjects. Finally, the proportion of CD127low TReg cells correlated inversely with HTLV-1 proviral load.
  
  
  CONCLUSIONS
  Taken together, the results suggest that TReg cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4+ T cells, in particular those expressing the CD25highCD127low phenotype. TReg cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. Jakob.michaelsson@ki.se
authors.forename: Jakob
authors.initials: J
authors.lastname: Michaëlsson
authors.forename: Hugo Marcelo R
authors.initials: HM
authors.lastname: Barbosa
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Jordan
authors.forename: Joan M
authors.initials: JM
authors.lastname: Chapman
authors.forename: Milena K C
authors.initials: MK
authors.lastname: Brunialti
authors.forename: Walter Kleine
authors.initials: WK
authors.lastname: Neto
authors.forename: Youko
authors.initials: Y
authors.lastname: Nukui
authors.forename: Ester C
authors.initials: EC
authors.lastname: Sabino
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Chieia
authors.forename: Acary Souza Bulle
authors.initials: AS
authors.lastname: Oliveira
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D015490:HTLV-I Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000209:etiology / Q000276:immunology* / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D019562:Viral Load
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D007371:Interferon-gamma