PLoS Neglected Tropical Diseases (Apr 2011)

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

  • Lishomwa C Ndhlovu,
  • Fabio E Leal,
  • Aaron M Hasenkrug,
  • Aashish R Jha,
  • Karina I Carvalho,
  • Ijeoma G Eccles-James,
  • Fernanda R Bruno,
  • Raphaella G S Vieira,
  • Vanessa A York,
  • Glen M Chew,
  • R Brad Jones,
  • Yuetsu Tanaka,
  • Walter K Neto,
  • Sabri S Sanabani,
  • Mario A Ostrowski,
  • Aluisio C Segurado,
  • Douglas F Nixon,
  • Esper G Kallas

DOI
https://doi.org/10.1371/journal.pntd.0001030
Journal volume & issue
Vol. 5, no. 4
p. e1030

Abstract

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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.