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

  • Fabio E Leal1, 2Email author,
  • Lishomwa C Ndhlovu3,
  • Aaron M Hasenkrug3,
  • Aashish R Jha3,
  • Karina I Carvalho1,
  • Ijeoma G Eccles-James3,
  • Fernanda R Bruno1,
  • Raphaella G Vieira3,
  • Vanessa A York3,
  • R Brad Jones4,
  • Yuetsu Tanaka5,
  • Walter K Neto6,
  • Sabri S Sanabani6,
  • Mario A Ostrowski4,
  • Aluisio C Segurado2,
  • Douglas F Nixon3 and
  • Esper G Kallas1, 2
Retrovirology20118(Suppl 1):A94

Published: 6 June 2011


Cytolytic ActivityUninfected ControlSpastic ParaparesisImmune ReceptorAltered Pattern


Most patients with HTLV-1 infection are asymptomatic, however 3% of individuals develop a progressive neurological disorder, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Factors leading to this complication are not well defined, but are associated with high levels of pro-virus and cytolytic T cells. During chronic viral infections, virus-specific CD8+ T cells undergo altered patterns of differentiation and can become restrained from effector activity. We hypothesized that suppression of immune receptors T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and PD-1 would result in partial reversal of a T cell restraint profile. In turn this increased cytolytic activity may mediate neuro-immunopathology of HAM/TSP.


We investigated the expression of Tim-3 and PD-1 on T cells in 22 serially recruited HTLV-1 asymptomatic and HAM/TSP patients and 7 HTLV-1-seronegative matched controls, their distribution on HTLV-1-specific T cells and the relationship with T cell function.


Using flow cytometry, we found that patients with HAM/TSP had significantly lower levels of Tim-3+ PD-1- expressing CD8+ (p=0.002) and CD4+ (p=0.004) T cells compared to healthy uninfected controls. HTLV-1 Tax11-19, HLA-A*02 restricted CD8+ T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. Furthermore, we found that the frequency of Tim-3 expressing Tax11-19 specific CD8+ T cells inversely correlated with the number of IFN-γ secreting cells in response to the Tax Tax11-19 peptide.


We propose that this low expression of Tim-3 on HTLV-1 Tax-specific T cells may lead to persistent and deleterious effector T cell pool, resulting in more inflammation and disease progression.

Authors’ Affiliations

Division of Clinical Immunology and Allergy School of Medicine, Universidade de Sao Paulo, Brazil
Department of Infectious Diseases School of Medicine Universidade de Sao Paulo, Sao Paulo, Brazil
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, USA
Department of Immunology , University of Toronto, Medical Sciences Building, King s College Circle, Toronto, Canada
Department of Immunology, University of the Ryukyus, Okinawa, Japan
Molecular Biology Laboratory, Fundação Pro-Sangue, Hemocentro de Sao Paulo, Sao Paulo, Brazil


© Leal et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.