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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

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Correspondence to Fabio E Leal.

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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 (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Leal, F.E., Ndhlovu, L.C., Hasenkrug, A.M. et al. HTLV-1 Tax Specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: implications for progression to neurological complications. Retrovirology 8, A94 (2011). https://doi.org/10.1186/1742-4690-8-S1-A94

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Keywords

  • Cytolytic Activity
  • Uninfected Control
  • Spastic Paraparesis
  • Immune Receptor
  • Altered Pattern