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

BMC Immunol. 2008 Jul 29:9:41. doi: 10.1186/1471-2172-9-41.

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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Proliferation
  • Female
  • Gene Expression Regulation / immunology
  • HTLV-I Infections / complications
  • HTLV-I Infections / immunology*
  • HTLV-I Infections / virology
  • Human T-lymphotropic virus 1 / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-7 Receptor alpha Subunit / biosynthesis
  • Interleukin-7 Receptor alpha Subunit / genetics
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Paraparesis, Tropical Spastic / etiology
  • Paraparesis, Tropical Spastic / immunology*
  • Paraparesis, Tropical Spastic / virology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / virology
  • Viral Load

Substances

  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit
  • Interferon-gamma