HTLV-1 modulates the frequency and phenotype of FoxP3+CD4+ T cells in virus-infected individuals

Retrovirology

Masao Matsuoka¹  Kisato Nosaka⁴  Masanori Nakagawa⁵  Junko Tanabe¹  Atae Utsunomiya²  Yorifumi Satou³ 

[1] Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, 606-8507, Japan;Department of Hematology, Imamura Bun-in Hospital, Kagoshima, 890-0064, Japan;Current address: Immunology Section, Division of Infectious Diseases, Department of Medicine, Imperial College, London, W2 1PG, UK;Department of Hematology, Kumamoto University School of Medicine, Kumamoto, 860-8556, Japan;Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan

关键词: HBZ;    Tax;    FoxP3;    HAM/TSP;    ATL;    HTLV-1;   

Others  :  1209297
DOI  :  10.1186/1742-4690-9-46

 received in 2011-12-24, accepted in 2012-05-30,  发布年份 2012

【 摘 要 】

Background

HTLV-1 utilizes CD4 T cells as the main host cell and maintains the proviral load via clonal proliferation of infected CD4⁺ T cells. Infection of CD4⁺ T cells by HTLV-1 is therefore thought to play a pivotal role in HTLV-1-related pathogenicity, including leukemia/lymphoma of CD4⁺ T cells and chronic inflammatory diseases. Recently, it has been reported that a proportion of HTLV-1 infected CD4⁺ T cells express FoxP3, a master molecule of regulatory T cells. However, crucial questions remain unanswered on the relationship between HTLV-1 infection and FoxP3 expression.

Results

To investigate the effect of HTLV-1 infection on CD4⁺ T-cell subsets, we used flow cytometry to analyze the T-cell phenotype and HTLV-1 infection in peripheral mononuclear cells (PBMCs) of four groups of subjects, including 23 HTLV-1-infected asymptomatic carriers (AC), 10 patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), 10 patients with adult T-cell leukemia (ATL), and 10 healthy donors. The frequency of FoxP3⁺ cells in CD4⁺ T cells in AC with high proviral load and patients with HAM/TSP or ATL was higher than that in uninfected individuals. The proviral load was positively correlated with the percentage of CD4⁺ T cells that were FoxP3⁺. The CD4⁺FoxP3⁺ T cells, themselves, were frequently infected with HTLV-1. We conclude that FoxP3⁺ T- cells are disproportionately infected with HTLV-1 during chronic infection. We next focused on PBMCs of HAM/TSP patients. The expression levels of the T_reg associated molecules CTLA-4 and GITR were decreased in CD4⁺FoxP3⁺ T cells. Further we characterized FoxP3⁺CD4⁺ T-cell subsets by staining CD45RA and FoxP3, which revealed an increase in CD45RA⁻FoxP3^low non-suppressive T-cells. These findings can reconcile the inflammatory phenotype of HAM/TSP with the observed increase in frequency of FoxP3⁺ cells. Finally, we analyzed ATL cells and observed not only a high frequency of FoxP3 expression but also wide variation in FoxP3 expression level among individual cases.

Conclusions

HTLV-1 infection induces an abnormal frequency and phenotype of FoxP3⁺CD4⁺ T cells.

【 授权许可】

   
2012 Satou et al.; licensee BioMed Central Ltd.

【 图 表 】

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