HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: implications for progression to neurological complications

PLoS Negl Trop Dis. 2011 Apr 26;5(4):e1030. doi: 10.1371/journal.pntd.0001030.

Abstract

The T cell immunoglobulin mucin 3 (Tim-3) receptor is highly expressed on HIV-1-specific T cells, rendering them partially "exhausted" and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis), we investigated the expression of the Tim-3 receptor on CD8(+) T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8(+) and CD4(+) T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8(+) T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3(+) and Tim-3(-) fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Gene Expression Profiling*
  • Gene Products, tax / immunology*
  • Hepatitis A Virus Cellular Receptor 2
  • Human T-lymphotropic virus 1 / immunology*
  • Humans
  • Male
  • Membrane Proteins / biosynthesis*
  • Middle Aged
  • Paraparesis, Tropical Spastic / immunology*
  • Paraparesis, Tropical Spastic / pathology*

Substances

  • Gene Products, tax
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Membrane Proteins
  • tax protein, Human T-lymphotrophic virus 1